Application of cellulose derivative-based hydrogel in tumor PDX model

Abstract

The invention relates to cellulose derivative matrigel and application thereof in a tumor CDX or PDX model, the cellulose derivative matrigel is a ready-to-use hydrogel free of animal-derived components, can be used for constructing an efficient and stable tumor CDX or PDX model, is simple to operate, has high similarity with clinical tumors, and can be used for preparing the tumor CDX or PDX model. And a solution is provided for clinical curative effect prediction and preclinical research.

Description

[0001] The present invention claims the priority benefit of the prior application filed by the applicant with the State Intellectual Property Office of China on April 15, 2024, with patent application number CN202410450787.5 and invention name “Application of a cellulose derivative-based hydrogel in a tumor PDX model”. The contents of the above application are incorporated into this text by reference. Technical Field

[0002] The present invention belongs to the field of biotechnology, and in particular relates to the application of a cellulose derivative matrix gel in a tumor CDX or PDX model. Background Art

[0003] A tumor is a neoplasm formed when a cell in a local tissue loses normal genetic regulation of its growth under the influence of various carcinogenic factors, leading to its clonal abnormal proliferation. It is generally believed that tumor cells are monoclonal, that is, all tumor cells in a tumor are descendants of a single mutated cell. The main malignant tumors in my country currently include gastric cancer, lung cancer, intestinal cancer, esophageal cancer, and breast cancer, which have high morbidity and mortality rates and poor prognosis. Currently, due to the lack of research models that characterize the occurrence and development characteristics of tumors such as gastric cancer, the research on the pathogenesis of gastric cancer and the development of therapeutic drugs are subject to certain limitations.

[0004] Traditional cell line models are the most commonly used models for human tumor research, but these models differ significantly from the human tumor microenvironment, resulting in lower predictive value in clinical trials. During the passage of traditional tumor cell lines, cellular characteristics undergo significant changes, such as the insertion and loss of genetic information, changes in growth and invasion characteristics, and the loss of specific cell populations. Tumor tissue is composed of highly heterogeneous subpopulations of cancer cells with different characteristics, and the tumor microenvironment is indispensable in the occurrence and development of tumors. Therefore, in clinical research, cell line tumor research models cannot represent the complex heterogeneity of tumors. For the above reasons, traditional cell line tumor research models cannot meet the needs of clinical tumor model research, especially in terms of the needs of tumor research translation.

[0005] The CDX model, known as Cell-Derived Xenograft (CDX), involves inoculating in vitro cultured tumor cells into immunodeficient mice. Due to its well-defined tumor growth kinetics, ease of genetic manipulation, high tumorigenicity, low cost, and ability to generate consistent and reproducible data, it is widely used in cancer research and anticancer drug development, and is a preferred model for in vivo drug screening. CDX models are typically inoculated subcutaneously, intravenously, intraarterially, or orthotopically.

[0006] The PDX model is called a patient-derived tumor xenograft model. Its full name is Patient-Derived tumorXenograft. It is a human-derived xenograft model established by directly transplanting the patient's tumor tissue into immunodeficient mice. This model is characterized by retaining most of the characteristics of the primary tumor at the histopathological, molecular biological and genetic levels. It has good predictive power for clinical efficacy and is widely used in new drug development, especially in patient screening for clinical trials of target drugs and research on predictive biomarkers. The PDX model is one of the most promising models. Studies have shown that the response of clinical patients to cytotoxic drugs is highly consistent with the results of the PDX model. The PDX model has high tumor heterogeneity, a short modeling time, and is close to the human tumor microenvironment. Therefore, this model has gradually become the preferred preclinical research tool.

[0007] The CDX or PDX model construction method requires the use of Matrigel. For example, the commonly used Matrigel is a basement membrane matrix extracted from EHS mouse tumors, which are rich in extracellular matrix proteins. Its main components include laminin, type IV collagen, heparin sulfate glycoprotein, and entactin, as well as various growth factors and matrix metalloproteinases. However, Matrigel currently has several issues: 1) supply shortages due to animal welfare concerns; 2) large and difficult-to-control batch-to-batch variability, with the nutrients and protein content being significantly affected by batch; 3) animal-derived proteins and nucleic acids can interfere with downstream experiments such as drug efficacy evaluation and fluorescence detection; and 4) the temperature sensitivity of Matrigel itself imposes stringent temperature requirements for storage and operation.

[0008] Currently, animal models of solid tumors cannot meet the needs of preclinical research, which hinders the prediction of clinical efficacy and preclinical research. Therefore, it is necessary to establish efficient and stable tumor CDX or PDX models. Summary of the Invention

[0009] In order to solve the above technical problems, the present invention uses cellulose derivatives as raw materials to prepare cellulose derivative matrix glue, which has incomparable advantages over animal-derived matrix glue in terms of performance, ease of use, batch-to-batch stability, process amplification stability, and automation compatibility. At the same time, a method for constructing a tumor CDX or PDX model using the above-mentioned cellulose derivative matrix glue is provided, and a human tumor xenograft model is constructed.

[0010] Specifically, the present invention provides the following technical solutions:

[0011] A cellulose derivative matrix glue, wherein the matrix of the cellulose derivative matrix glue is a cellulose derivative.

[0012] According to an embodiment of the present invention, the cellulose derivative includes cellulose ester, cellulose ether, oxidized cellulose, charged cellulose or other types of cellulose derivatives.

[0013] According to some embodiments of the present invention, the cellulose ester includes cellulose monoester or cellulose mixed ester.

[0014] According to some embodiments of the present invention, the cellulose monoester includes cellulose organic acid ester or cellulose inorganic acid ester.

[0015] According to some embodiments of the present invention, the cellulose organic acid ester includes cellulose methyl ester, cellulose ethyl ester, cellulose propyl ester, cellulose butyl ester, to cellulose octadecyl ester and other saturated and unsaturated fatty acid esters; aromatic esters such as cellulose benzoate, cellulose lactate, cellulose citrate, cellulose carbamate, cellulose cyclohexylcarboxylate, cellulose cinnamate or cellulose 2-methylbenzoate, etc.

[0016] According to some embodiments of the present invention, the inorganic cellulose acid ester includes cellulose phosphate, cellulose sulfate, cellulose nitrate, or the like.

[0017] According to some embodiments of the present invention, the cellulose mixed ester includes cellulose acetate butyrate CAB, cellulose acetate propionate CAP, cellulose acetate 2-methylbenzoate mixed ester, cellulose 2-methylbenzoate-4-trifluoromethylbenzoate mixed ester or cellulose acetate adamantanecarboxylate mixed ester, etc.

[0018] According to some embodiments of the present invention, the cellulose ether includes cellulose monoether or cellulose mixed ether.

[0019] According to some embodiments of the present invention, the cellulose ether includes methyl cellulose MC, ethyl cellulose AC, propyl cellulose PC or carboxymethyl cellulose CMC.

[0020] According to some embodiments of the present invention, the cellulose mixed ether includes hydroxymethyl cellulose HMC, hydroxypropyl cellulose HPC or hydroxypropyl methyl cellulose HPMC.

[0021] According to some embodiments of the present invention, the oxidized cellulose includes dialdehyde cellulose, glycol cellulose, dicarboxyl cellulose, or the like.

[0022] According to some embodiments of the present invention, the charged cellulose includes cationic cellulose or anionic cellulose and salts thereof.

[0023] According to some embodiments of the present invention, the cationic cellulose includes a quaternary ammonium group, an imidazole group or a pyridyl group.

[0024] According to some embodiments of the present invention, the anionic cellulose includes carboxyl, hydroxide, sulfate, phosphate, etc., and the anionic cellulose salt includes sodium salt, potassium salt, calcium salt, magnesium salt, iron salt or ammonium salt, etc.

[0025] According to some embodiments of the present invention, other cellulose derivatives include cellulose containing a DOPO structure, alkylated cellulose, aminated cellulose, chlorinated cellulose, amidated cellulose, silanized cellulose, or plasma-modified cellulose.

[0026] According to some embodiments of the present invention, the degree of substitution of the cellulose derivative is 0.1 to 3, preferably 0.5 to 2.5, and more preferably 1.0 to 2.0.

[0027] According to an embodiment of the present invention, the fiber diameter of the cellulose derivative is 0.01 μm to 0.10 μm, for example, 0.01 μm, 0.02 μm, 0.03 μm, 0.04 μm, 0.05 μm, 0.06 μm, 0.07 μm, 0.08 μm, 0.09 μm or 0.10 μm.

[0028] According to an embodiment of the present invention, the cellulose derivative matrix glue comprises a network structure composed of ultrafine fibers, exhibiting a highly ordered three-dimensional micro-nanostructure. The inventors have discovered that the network structure of the cellulose derivative of the present invention is more suitable for 3D culture, and the resulting matrix glue exhibits enhanced transparency, making it more convenient to observe cell status.

[0029] According to an embodiment of the present invention, the particle size of the matrix in the matrix gel is 1 μm-50 μm, for example, 1 μm 5 μm, 8 μm, 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 35 μm, 40 μm, 45 μm or 50 μm.

[0030] According to an embodiment of the present invention, the solid content of the matrix glue is 0.1-3.0 wt%, for example, 0.1 wt%, 0.5 wt%, 1 wt%, 1.5 wt%, 2 wt%, 2.5 wt% or 3.0 wt%.

[0031] The present invention provides a method for preparing the above-mentioned cellulose derivative matrix glue, which is selected from the following scheme 1 or scheme 2:

[0032] Option 1:

[0033] 1) Cellulose pretreatment;

[0034] 2) homogeneously or heterogeneously derivatizing cellulose to obtain cellulose derivatives;

[0035] 3) The cellulose derivative prepared in step 2) is prepared into a solution, and poured into a coagulation bath to form a cellulose derivative matrix glue.

[0036] According to an embodiment of the present invention, in step 1), the cellulose pretreatment includes dispersing the cellulose in a solvent, which can be water, DMF, ethanol or isopropanol, etc., and the cellulose can be microcrystalline cellulose, cotton pulp, wood pulp, inulin, soluble starch or dextran, etc., preferably wood pulp; or the cellulose pretreatment includes adding the cellulose to a cellulose solvent to form a cellulose solution.

[0037] According to an embodiment of the present invention, step 1) further comprises adding a certain amount of alkali to activate the cellulose, and the alkali can be sodium hydroxide, potassium hydroxide, sodium carbonate or sodium borohydride.

[0038] According to an embodiment of the present invention, in step 3), the solvent used to prepare the solution can be water, ethanol, acetone, DMF or NaOH aqueous solution.

[0039] Option 2:

[0040] 1) dissolving cellulose with a cellulose solvent;

[0041] 2) pouring the cellulose solution obtained in step 1) into a coagulation bath to form a cellulose gel;

[0042] 3) Derivatizing the cellulose gel obtained in step 2) to obtain a cellulose derivative matrix gel.

[0043] According to an embodiment of the present invention, in the scheme 1 and scheme 2, the cellulose solvent is any good solvent known in the art that can dissolve (the dissolution includes complete dissolution and partial dissolution) cellulose. Preferably, it can be selected from one or more of the following systems: copper ammonia solution, copper ethylenediamine solution, organic solvent, ionic liquid, ionic liquid and organic solvent mixed solvent, choline type ionic liquid deep eutectic solvent system, organic solvent / salt system, amine oxide system (NMMO), carbamate system, alkali / water system, alkali / urea system, alkali / thiourea system, liquid ammonia / NH4SCN, organic acid, metal salt aqueous solution, alcohol solution of metal salt hydrate, water-alcohol mixed solution of metal salt hydrate and other solvent systems.

[0044] The organic solvent may be selected from one or more of N,N-dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAc), N-methyl-2-pyrrolidone (NMP), N-methylimidazole, imidazole, pyridine, ethylenediamine, hexafluoroacetone, hexafluoroisopropanol, glycerol, methyl isobutyl ketone, tetrahydrofuran, dioxane, and γ-valerolactone (GVL).

[0045] The organic solvent / salt system can be selected from one or more of N,N-dimethylacetamide / lithium chloride (DMAc / LiCl) system, N-methyl-2-pyrrolidone / NMP, and N,N-dimethyl sulfoxide / tetrabutylammonium fluoride system (DMSO / TBAF).

[0046] The alkali / water system can be selected from one or both of NaOH / H2O and KOH / H2O.

[0047] Wherein, the alkali / urea system can be selected from NaOH / Urea.

[0048] Wherein, the alkaline / thiourea system is selected from NaOH / thio-urea.

[0049] The organic acid can be selected from one or more of formic acid, acetic acid, propionic acid, butyric acid, succinic acid, lactic acid, glutamic acid, glycine, dichloroacetic acid, trichloroacetic acid, and toluenesulfonic acid.

[0050] Among them, the metal salt aqueous solution is preferably selected from aqueous solutions of metal salts such as CaCl2, ZnCl2, LiClO4, Ca(SCN)2, and LiSCN.

[0051] The alcohol solution of the metal salt hydrate can be selected from a methanol solution of CaBr2·H2O and a methanol solution of CaCl2·2H2O.

[0052] The water-alcohol mixed solution of the metal salt hydrate can be selected from a methanol aqueous solution of CaBr2·H2O and a methanol aqueous solution of CaCl2·2H2O.

[0053] The amine oxide system may be a NMMO / H2O / DMSO system, a NMMO / H2O / diethyltriamine system, or a NMMO / H2O system.

[0054] The ionic liquid is selected from an organic molten salt formed by cations and anions with a melting point lower than 100° C., preferably an organic molten salt that can dissolve the biomass natural polymer.

[0055] For example, the cation of the ionic liquid is selected from one or more substituted or unsubstituted imidazole, pyridine, pyrrole, amine, phosphine, choline, diazabicyclic, amino acid type cations; for example, the substituent can be C 1-6 Alkyl, C 1-6 One or more of alkenyl, phenyl or substituted phenyl; preferably one or more of methyl, ethyl, butyl and allyl;

[0056] Preferably, the cation is selected from one or more of the following cations: 1-ethyl-3-methylimidazolium cation ([EMIM]), 3-methylimidazolium cation ([MIM]), 1-propyl-3-methylimidazolium cation ([PMIM]), 1-allyl-3-methylimidazolium cation ([AMIM]), 1-butyl-3-methylimidazolium cation ([BMIM]), 1-butyl-2,3-dimethylimidazolium cation ([BMMIM]), 1,3-dimethylimidazolium cation ([MMIM]), 1-methoxyethyl-3-methylimidazolium cation ([MeOEMIM]), 1-methoxymethyl-3-methylimidazolium cation ([MeOMMIM]), 1-hydroxy-3-methylimidazolium cation ([HMIM]), 1-(2-hydroxyethyl)-3-methylimidazolium cation ([HOEMIM]), 1-methyl-3-benzylimidazolium cation ([MBzIM]), 1 cations include 1-pentyl-3-methylimidazolium cation ([PeMIM]), 1-benzyl-3-methylimidazolium cation ([BzMIM]), 1-m-methoxybenzyl-3-methylimidazolium cation ([MeOBzMIM]), 1-m-methylbenzyl-3-methylimidazolium cation ([MeBzMIM]), N-methylpyridinium cation ([MPyr]), N-ethylpyridinium cation ([EPyr]), N-butylpyridinium cation ([BPyr]), N-n-hexylpyridinium cation ([HPyr]), 1-butyl-3-methylpyrrolidinium ion ([BMPyrr]), tris(2-hydroxyethyl)methylamine ([THEMA]), tetrabutylamine ([TBA]), tetrabutylphosphine ([PBu4]), glycine cation ([Gly]), choline cation ([Ch]), and 1,5-diazabicyclo[4.3.0]one-5-ene ([DBNH]).

[0057] More preferably, the cation is selected from one or more of the following cations: 1-ethyl-3-methylimidazolium cation ([EMIM]), 1-allyl-3-methylimidazolium cation ([AMIM]), 1-butyl-3-methylimidazolium cation ([BMIM]), choline cation ([Ch]).

[0058] For example, the anion is selected from one or more of halogen anions, organic acid radical ions, organic acid ester anions, amino acid type anions, and the like.

[0059] Preferably, the anion is selected from one or more of the following anions: chloride ([Cl]), bromide ([Br]), fluoride ([F]), formate ([HCOO]), acetate ([CH3COO] or [Ac]), glycolate ([HOCH2COO]), propionate ([CH3CH2COO] or [OPr]), butyrate ([CH3CH2CH2COO] or [OBu]), octanoate ([Oct]), benzoate ([C6H5COO] or [PhCOO]), lactate ([CH3CH(OH)COO] or [Lac]), thioglycolate ([HSCH2COO]) , hexafluorophosphate ion ([PF6]), trifluoroborate ([BF3]), methyl phosphate ion ([(MeO)HPO2] or [MP]), dimethyl phosphate ion ([(MeO)2PO2] or [DMP]), diethyl phosphate ion ([(EtO)2PO2] or [DEP]), methyl sulfonate anion ([MeOSO3]), trifluoromethylsulfonate anion ([CF3SO3]), glycine anion ([Gly]), lysine anion ([Lys]), valine anion ([Val]), dicyanamide anion ([N(CN)2] or [DCA]), bistrifluoromethylsulfonimide ([Tf2N]) and the like anion or more.

[0060] More preferably, the anion is selected from one or more of the following anions: chloride ion ([Cl]), formate ion ([HCOO]), acetate ion ([Ac]), methyl phosphate ion ([(MeO)HPO2] or [MP]), dimethyl phosphate ion ([(MeO)2PO2] or [DMP]) and dicyanamide anion ([N(CN)2] or [DCA]).

[0061] According to some embodiments of the present invention, the ionic liquid can be selected from one or more of the following ionic liquids: 1-ethyl-3-methylimidazolium chloride ionic liquid ([EMIM][Cl]), 1-ethyl-3-methylimidazolium bromide ionic liquid ([EMIM][Br]), 1-ethyl-3-methylimidazolium formate ionic liquid ([EMIM][HCOO]), 1-ethyl-3-methylimidazolium acetate ionic liquid ([EMIM][Ac]), 1-ethyl-3-methylimidazolium octanoate ionic liquid ([EMIM][Oct]), 1-ethyl-3-methylimidazolium methyl phosphate ionic liquid ([EMIM][MP]), 1-ethyl-3-methylimidazolium dimethyl phosphate ionic liquid ([EMIM][MP]), Ionic liquids ([EMIM][DMP]), 1-ethyl-3-methylimidazolium diethyl phosphate ionic liquid ([EMIM][DEP]), 1-ethyl-3-methylimidazolium propionate ionic liquid ([EMIM][OPr]), 1-ethyl-3-methylimidazolium top ionic liquid ([EMIM][OBu]), 1-ethyl-3-methylimidazolium glycinate ionic liquid ([EMIM][Gly]), 1-ethyl-3-methylimidazolium lysine ionic liquid ([EMIM][Lys]), 1-allyl-3-methylimidazolium chloride ionic liquid ([AMIM][Cl]), 1-allyl-3-methylimidazolium bromide ionic liquid ([AMIM][Br]) , 1-allyl-3-methylimidazolium formate ionic liquid ([AMIM][HCOO]), 1-allyl-3-methylimidazolium acetate ionic liquid ([AMIM][Ac]), 1-butyl-3-methylimidazolium chloride ionic liquid ([BMIM][Cl]), 1-butyl-3-methylimidazolium bromide ionic liquid ([BMIM][Br]), 1-butyl-3-methylimidazolium formate ionic liquid ([BMIM][HCOO]), 1-butyl-3-methylimidazolium acetate ionic liquid ([BMIM][Ac]), 1-butyl-3-methylimidazolium hydroxyacetate ionic liquid ([BMIM][HOCH2COO]), 1-butyl-3-methylimidazolium propionate ionic liquid ionic liquid ([BMIM][CH3CH2COO]), 1-butyl-3-methylimidazolium lactate ionic liquid [BMIM][Lac], 1-butyl-3-methylimidazolium butyrate ionic liquid ([BMIM][CH3CH2CH2COO]), 1-butyl-3-methylimidazolium benzoate ionic liquid ([BMIM][C6H5COO]), 1-butyl-3-methylimidazolium glycine ionic liquid ([BMIM][H2NCH2COO]), 1-butyl-3-methylimidazolium dicyanamide ionic liquid ([BMIM][N(CN)2]), 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquid ([BMIM][Tf2N]),1-Butyl-3-methylimidazolium hexafluorophosphate ionic liquid ([BMIM][PF6]), 1-Butyl-3-methylimidazolium tetrafluoroborate ionic liquid ([BMIM][BF4]), 1-Butyl-3-methylimidazolium methanesulfonate ionic liquid ([BMIM][MeOSO3]), 1-Butyl-3-methylimidazolium trifluoromethylsulfonate ionic liquid ([BMIM][CF3SO3]), 1-Butyl-2,3-dimethylimidazolium tetrafluoroborate ionic liquid ([BMMIM][BF4]), 3-Methylimidazolium formate ionic liquid ([MIM][HCOO]), 1,3-Dimethylimidazolium chloride ionic liquid ([MMIM][Cl]), 1,3-Dimethyl 1-(2-hydroxyethyl)-3-methylimidazolium chloride ionic liquid ([HOEMIM][Cl]), 1-methoxymethyl-3-methylimidazolium bromide ionic liquid ([MeOMMIM][Br]), 1-methoxyethyl-3-methylimidazolium chloride ionic liquid ([HMIM][Cl]), 1-hydroxy-3-methylimidazolium trifluoromethylsulfonate ionic liquid ([HMIM][CF3SO3]), 1-(2-hydroxyethyl)-3-methylimidazolium chloride ionic liquid ([HOEMIM][Cl]), 1-methoxymethyl-3-methylimidazolium bromide ionic liquid ([MeOMMIM][Br]), 1-methoxyethyl-3-methylimidazolium chloride ionic liquid ([HMIM][Cl]), 1-methoxyethyl ...methoxyethyl-3-methylimidazolium chloride 3-Methylimidazolium bromide ionic liquid ([MeOEMIM][Br]), N-ethylpyridinium chloride ionic liquid ([EPyr][Cl]), N-ethylpyridinium bromide ionic liquid ([EPyr][Br]), N-methylpicolinate ionic liquid ([MPyr][HCOO]), tris(2-hydroxyethyl)methylamine acetate ionic liquid ([THEMA][Ac]), tris(2-hydroxyethyl)methylamine methanesulfonate ionic liquid ([THEMA][MeOSO3]), tris(2-hydroxyethyl)methylamine trifluoromethanesulfonate ionic liquid [THEMA][CF3SO3], tetrabutylphosphine valine ionic liquid [PBu4][Val], tetrabutylphosphine lysate Amine salt ionic liquid [PBu4][Lys], tetrabutylphosphine glycinate ionic liquid [PBu4][Gly], 1-benzyl-3-methylimidazolium chloride ionic liquid ([BzMIM][Cl]), 1-benzyl-3-methylimidazolium dicyanamide ionic liquid ([BzMIM][DCA]), 1-m-methylbenzyl-3-methylimidazolium chloride ionic liquid ([MeBzMIM][Cl]), 1-m-methoxybenzyl-3-methylimidazolium chloride ionic liquid ([MeOBzMIM][Cl]), choline chloride ionic liquid ([Ch][Cl]), choline bromide ionic liquid (Ch][Br]), choline acetate ionic liquid ([Ch][CH3COO]),Ionic liquids include choline propionate ionic liquid ([Ch][CH3CH2COO]), choline butyrate ionic liquid ([Ch][CH3CH2CH2COO]), glycine hydrochloride ionic liquid ([Gly][Cl]), 1,5-diazabicyclo[4.3.0]keto-5-ene acetate ionic liquid ([DBNH][Ac]), etc.

[0062] Preferably, the choline-type deep eutectic solvent system is selected from one or more of [Ch][Cl] / urea, [Ch][Br] / urea, [Ch][Cl] / thio-urea, [Ch][Cl] / glycerol, and [Ch][Cl] / lactic acid.

[0063] Preferably, the solvent system for dissolving cellulose is selected from the ionic liquid and / or NaOH / Urea system; more preferably, the cellulose-dissolving ionic liquid is selected from one or more of [AMIM][Cl], [BMIM][Cl], [EMIM][Ac], and [BMIM][Ac].

[0064] According to some embodiments of the present invention, in Scheme 1 and Scheme 2, the solid content of the cellulose derivative matrix glue is 0.1-3.0 wt%, for example, 0.1 wt%, 0.5 wt%, 1 wt%, 1.5 wt%, 2 wt%, 2.5 wt% or 3.0 wt%.

[0065] The present invention also provides a method for constructing a tumor CDX or PDX model using the cellulose derivative matrix gel.

[0066] The present invention also provides a tumor CDX or PDX model obtained according to the method.

[0067] The present invention also provides an application of the tumor CDX or PDX model in personalized precision diagnosis and treatment, preclinical drug screening of new anticancer drugs, and tumor disease research.

[0068] According to an embodiment of the present invention, the tumor is preferably a human gastric cancer tumor, a human intestinal cancer tumor, a human lung cancer tumor, a human pancreatic cancer tumor, a human breast cancer tumor or a human colon cancer tumor.

[0069] According to an embodiment of the present invention, the method for constructing the tumor CDX model comprises the following steps:

[0070] a) Tumor cell preparation;

[0071] b) Tumor cell mixing: Tumor cells were mixed in cellulose matrix gel;

[0072] c) Tumor cells mixed with a cellulose derivative, Matrigel, were transplanted into mice.

[0073] According to an embodiment of the present invention, preferably, the cellulose derivative matrix gel and the cell suspension are uniformly mixed in a ratio of 1:1.

[0074] According to an embodiment of the present invention, the method for constructing the tumor PDX model comprises the following steps:

[0075] a) Tumor tissue preparation;

[0076] b) Tumor tissue mixed with a cellulose derivative, Matrigel;

[0077] c) The tumor group mixed with the cellulose derivative Matrigel was transplanted into mice.

[0078] Beneficial effects of the present invention:

[0079] 1) The present invention uses cellulose derivatives as raw materials to prepare Matrigel, which is a ready-to-use Matrigel that does not contain animal-derived ingredients. Compared with animal-derived Matrigel, it has incomparable advantages in performance, ease of use, batch-to-batch stability, process scale-up stability, and automation compatibility.

[0080] 2) The present invention provides a method for constructing a tumor CDX or PDX model, which constructs an efficient and stable tumor CDX or PDX model, overcomes the difficulties of limited animal models in clinical tumor research and treatment, has a high similarity with clinical tumors, has a high tumor formation rate after tumor cell transplantation, and retains the original microenvironment of the tumor tissue. The construction method is simple and the cost is low. It can be widely used in personalized precision diagnosis and treatment, preclinical drug screening of new anti-cancer drugs and tumor disease research.

[0081] The present invention proposes a cellulose matrix gel prepared from cellulose derivatives, which can be used to construct tumor CDX or PDX models to form a favorable microenvironment for tumor growth. Its advantages are as follows:

[0082] 1) Non-animal origin, with clear ingredients, and potential applications in clinical, pharmaceutical, cell, and stem cell industrial scenarios and research;

[0083] 2) Batch stability: standardized production and strict quality control can ensure batch stability;

[0084] 3) Ready-to-use, stored at room temperature, ready for use at any time, no gel preparation steps required, just mix with cells;

[0085] 4) One-step cell recovery: a gentle one-step enzymatic process is used to recover organoids without any impact on the organoids;

[0086] 5) The expression of proteins and gene mutations in tissues / organs in vivo can be preserved;

[0087] 6) Can be cultured to form tissue-like and organoid functions similar to those in vivo;

[0088] 7) The tumor organoid structures formed in culture are non-vacuolated and mostly solid;

[0089] 8) Can be vascularized, immune co-cultured, etc.

[0090] 9) Provide a standard and effective 3D platform for organoid research and industrialization.

[0091] The cellulose derivative matrix gel of the present invention can be used to construct an efficient and stable tumor CDX or PDX model, is simple to operate, and has a high similarity with clinical tumors. DETAILED DESCRIPTION

[0092] The technical solutions of the present invention will be described in further detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explain the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are encompassed within the scope of protection that the present invention is intended to protect.

[0093] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0094] The "cellulose derivative-based hydrogel" in the present invention may have the same meaning as "cellulose derivative-based matrix gel".

[0095] The present invention provides a method for constructing a tumor CDX or PDX model using a cellulose derivative matrix gel, thereby constructing a human tumor xenograft model.

[0096] The present invention will be further described below by means of specific embodiments:

[0097] 1. Preparation Example 1

[0098] (1) Preparation of cellulose ether matrix glue:

[0099] 1) Preparation of Methylcellulose MC Matrigel

[0100] 20g of wood pulp is dispersed in a solvent, which can be water, DMF, ethanol, or isopropanol. A certain amount of alkali is added to activate the cellulose for 30 minutes. The alkali can be sodium hydroxide, potassium hydroxide, sodium carbonate, or sodium borohydride. Then, a certain amount of dimethyl sulfate is added. The molar ratio of dimethyl sulfate to cellulose can be 1:1, 2:1, 3:1, or 4:1. The reaction is allowed to react at room temperature for 24 hours. Aqueous acetic acid is added to neutralize the alkali in the reaction solution. The reaction solution is filtered, and the resulting filter cake is washed 6-8 times with a solution such as water, ethanol, acetone, DMF, or aqueous NaOH to remove residual impurities. The washed methylcellulose is dispersed in pure water at a water to methylcellulose mass ratio of 9:1. The gel is then pulverized and further ground using a colloid mill or high-pressure homogenizer to a particle size of 1-50 μm and a solids content of 0.1-3.0 wt%. After autoclaving, Matrigel MC-1, MC-2, MC-3, and MC-4 are obtained.

[0101] 2) Preparation of Ethylcellulose EC Matrix Gel

[0102] Disperse 20g of wood pulp in a solvent, which can be water, DMF, ethanol, or tetrahydrofuran. Add a certain amount of alkali to activate the cellulose for 30 minutes. The alkali can be sodium hydroxide, potassium hydroxide, sodium carbonate, or sodium borohydride. Then, add a certain amount of ethylating agent, which can be ethyl bromide, ethyl chloride, chloroacetyl chloride, or diethyl sulfate. The molar ratio of ethylating agent to cellulose is set at 1:1, 2:1, 3:1, or 4:1. The reaction is allowed to proceed at room temperature for 24 hours. Aqueous acetic acid is then added to neutralize the alkali in the reaction solution. The reaction solution is filtered, and the resulting filter cake is washed 6-8 times with a solution, such as water, ethanol, acetone, DMF, or aqueous NaOH solution, to remove any residual impurities. The washed ethyl cellulose was dispersed in pure water with a water to ethyl cellulose mass ratio of 9:1. The gel was then crushed and pulverized using a colloid mill, high-pressure homogenizer, etc. to a particle size of 1-50 μm and a solid content of 0.1-3.0 wt%. After high-pressure sterilization, the matrix gels EC-1, EC-2, EC-3, and EC-4 were obtained.

[0103] 3) Preparation of Hydroxypropyl Cellulose (HPC) Matrix Gel

[0104] Disperse 20g of wood pulp in a solvent such as water, DMF, ethanol, or tetrahydrofuran. Add a certain amount of alkali to activate the cellulose for 2 hours. The alkali can be sodium hydroxide, potassium hydroxide, sodium carbonate, or sodium borohydride. Then, add a certain amount of propylene oxide, with a molar ratio of propylene oxide to cellulose set at 1:1, 2:1, 3:1, or 4:1. React at 80°C for 8 hours. After the reaction is complete, cool to room temperature, and then add aqueous acetic acid to neutralize the alkali in the reaction solution. Filter the reaction solution, and wash the resulting filter cake 6-8 times with a solution such as water, ethanol, acetone, DMF, or aqueous NaOH to remove any remaining impurities. The washed hydroxypropyl cellulose was dispersed in pure water with a mass ratio of water to hydroxypropyl cellulose of 9:1. The gel was then crushed and pulverized using a colloid mill, high-pressure homogenizer, or the like to a particle size of 1-50 μm and a solid content of 0.1-3.0 wt%. After high-pressure sterilization, matrix gels HPC-1, HPC-2, HPC-3, and HPC-4 were obtained.

[0105] 4) Preparation of Carboxymethyl Cellulose (CMC) Matrigel

[0106] Disperse 20g of wood pulp in a solvent such as water, isopropanol, ethanol, or tetrahydrofuran. Add a certain amount of alkali to activate the cellulose for 2 hours. The alkali can be sodium hydroxide, potassium hydroxide, sodium carbonate, or sodium borohydride. Then, add 11.6g of chloroacetic acid, with a molar ratio of alkali to chloroacetic acid set at 0.5:1, 1:1, 1.5:1, or 2:1. React at 70°C for 8 hours. After the reaction is complete, cool to room temperature, and then add aqueous acetic acid to neutralize the alkali in the reaction mixture. Filter the reaction mixture, and wash the resulting filter cake 6-8 times with a solution such as water, ethanol, acetone, DMF, or aqueous NaOH to remove any remaining impurities. The washed carboxymethyl cellulose was dispersed in pure water with a mass ratio of water to carboxymethyl cellulose of 9:1. The gel was then crushed and pulverized using a colloid mill, high-pressure homogenizer, or the like to a particle size of 1-50 μm and a solid content of 0.1-3.0 wt%. After high-pressure sterilization, the matrix gels CMC-1, CMC-2, CMC-3, and CMC-4 were obtained.

[0107] (2) Preparation of cellulose ester matrix glue

[0108] 1) Preparation of Cellulose Propionate Matrix Gel

[0109] Weigh 4.0 g of cellulose, which may be microcrystalline cellulose, cotton pulp, wood pulp, inulin, soluble starch, or dextran, and add it to 46 g of ionic liquid, which may be 1-allyl-3-methylimidazole propionate ([Amim][CH3CH2COO]), 1-ethyl-3-methylimidazole butyrate ([Emim][CH3CH2CH2COO]), 1-butyl-3-methylimidazole cyclohexylcarboxylate ([Bmim][ChCOO]), 1-butyl 3-Methylimidazolium cinnamate ([Bmim][CCOO]) and 1-butyl-3-methylimidazolium chloride (BmimCl) were stirred at 80°C for 30 minutes to obtain an 8 wt% solution. A certain amount of propionic anhydride was added to the solution at a molar ratio of propionic anhydride to cellulose of 1:1, 2:1, 3:1, and 4:1 at 80°C and stirred for 2 hours. The reaction solution was poured into water for precipitation and the product was washed 6-8 times with a solution such as water, ethanol, DMF, or aqueous NaOH to remove residual impurities. The washed cellulose propionate gel was dispersed in pure water at a water to cellulose propionate gel mass ratio of 9:1. The gel was then crushed and pulverized using a colloid mill, high-pressure homogenizer, or the like to a particle size of 1-50 μm and a solid content of 0.1-3.0 wt%. The cellulose propionate matrix gel was then sterilized by autoclave.

[0110] 2) Preparation of Cellulose Butyrate Matrix Gel

[0111] Weigh 4.0 g of cellulose, which may be microcrystalline cellulose, cotton pulp, wood pulp, inulin, soluble starch, or dextran, and add it to 46 g of ionic liquid, which may be 1-allyl-3-methylimidazole propionate ([Amim][CH3CH2COO]), 1-ethyl-3-methylimidazole butyrate ([Emim][CH3CH2CH2COO]), 1-butyl-3-methylimidazole cyclohexylcarboxylate ([Bmim][ChCOO]), 1-butyl 3-Methylimidazolium cinnamate ([Bmim][CCOO]) and 1-butyl-3-methylimidazolium chloride (BmimCl) were stirred at 80°C for 30 minutes to obtain an 8 wt% solution. A certain amount of butyric anhydride was added to the solution at a molar ratio of butyric anhydride to cellulose of 1:1, 2:1, 3:1, and 4:1 at 80°C and stirred for 2 hours. The reaction solution was poured into water for precipitation. The product was washed 6-8 times with a solution of water, ethanol, DMF, or aqueous NaOH to remove residual impurities. The washed cellulose butyrate gel was dispersed in pure water at a water to cellulose butyrate gel mass ratio of 9:1. The gel was then crushed using a colloid mill, high-pressure homogenizer, or other equipment to a particle size of 1-50 μm and a solids content of 0.1-3.0 wt%. After autoclaving, the cellulose butyrate matrix gel was obtained.

[0112] 3) Preparation of Cellulose Benzoate Matrix Gel

[0113] Weigh 4.0 g of cellulose, which may be microcrystalline cellulose, cotton pulp, wood pulp, inulin, soluble starch, or dextran, and add it to 46 g of ionic liquid, which may be 1-allyl-3-methylimidazole propionate ([Amim][CH3CH2COO]), 1-ethyl-3-methylimidazole butyrate ([Emim][CH3CH2CH2COO]), 1-butyl-3-methylimidazole cyclohexylcarboxylate ([Bmim][ChCOO]), 1-butyl- 3-Methylimidazolium cinnamate ([Bmim][CCOO]) and 1-butyl-3-methylimidazolium chloride (BmimCl) are stirred at 80°C for 30 minutes to obtain an 8 wt% solution. Benzoyl chloride is added to the solution at a molar ratio of benzoyl chloride to cellulose of 1:1, 2:1, 3:1, and 4:1 at 80°C and stirred for 2 hours. The reaction solution is poured into water for precipitation and the product is washed 6-8 times with a solution such as water, ethanol, DMF, or aqueous NaOH to remove residual impurities. The washed cellulose benzoate gel is dispersed in pure water at a water to cellulose benzoate ratio of 9:1. The gel is then crushed using a colloid mill, high-pressure homogenizer, or the like to a particle size of 1-50 μm and a solids content of 0.1-3.0 wt%. The resulting cellulose benzoate matrix gel is then sterilized by autoclaving.

[0114] 4) Preparation of Cellulose Cyclohexylcarboxylate Matrix Gel

[0115] Weigh 4.0 g of cellulose, which may be microcrystalline cellulose, cotton pulp, wood pulp, inulin, soluble starch, or dextran, and add it to 46 g of ionic liquid, which may be 1-allyl-3-methylimidazole propionate ([Amim][CH3CH2COO]), 1-ethyl-3-methylimidazole butyrate ([Emim][CH3CH2CH2COO]), 1-butyl-3-methylimidazole cyclohexylcarboxylate ([Bmim][Ch ... Methylimidazole cinnamate ([Bmim][CCOO]) and 1-butyl-3-methylimidazolium chloride (BmimCl) are stirred at 80°C for 30 minutes to obtain an 8 wt% solution. A certain amount of cyclohexylcarbonyl chloride is added to the solution at a molar ratio of cyclohexylcarbonyl chloride to cellulose of 1:1, 2:1, 3:1, or 4:1 at 80°C and stirred for 2 hours. The reaction solution is poured into water for precipitation and the product is washed 6-8 times with a solution such as water, ethanol, DMF, or aqueous NaOH to remove residual impurities. The washed cellulose cyclohexylcarbonyl gel is dispersed in pure water at a weight ratio of 9:1. The gel is then crushed using a colloid mill or high-pressure homogenizer to a particle size of 1-50 μm and a solids content of 0.1-3.0 wt%. The resulting cellulose cyclohexylcarbonyl matrix is ​​then sterilized by autoclaving.

[0116] 5) Preparation of Cellulose Cinnamate Matrix Gel

[0117] Weigh 4.0 g of cellulose, which may be microcrystalline cellulose, cotton pulp, wood pulp, inulin, soluble starch, or dextran, and add it to 46 g of ionic liquid, which may be 1-allyl-3-methylimidazole propionate ([Amim][CH3CH2COO]), 1-ethyl-3-methylimidazole butyrate ([Emim][CH3CH2CH2COO]), 1-butyl-3-methylimidazole cyclohexylcarboxylate ([Bmim][ChCOO]), 1-butyl- 3-Methylimidazole cinnamate ([Bmim][CCOO]) and 1-butyl-3-methylimidazole chloride (BmimCl) are stirred at 80°C for 30 minutes to obtain an 8 wt% solution. Cinnamoyl chloride is added to the solution at a molar ratio of cinnamoyl chloride to cellulose of 1:1, 2:1, 3:1, and 4:1 at 80°C and stirred for 2 hours. The reaction solution is poured into water for precipitation and the product is washed 6-8 times with a solution such as water, ethanol, DMF, or aqueous NaOH to remove residual impurities. The washed cellulose cinnamoyl ester gel is dispersed in pure water at a water-to-cellulose cinnamoyl ester gel weight ratio of 9:1. The gel is then crushed using a colloid mill, high-pressure homogenizer, or other similar equipment to a particle size of 1-50 μm and a solids content of 0.1-3.0 wt%. The product is then sterilized by autoclave to obtain a cellulose cinnamoyl ester matrix gel.

[0118] 6) Preparation of Cellulose 2-Methylbenzoate Matrix Gel

[0119] Weigh 8g of cellulose. The cellulose that can be used includes microcrystalline cellulose, wood pulp, and cotton pulp, and dissolve it in 92g of ionic liquid. The ionic liquid can be 1-allyl-3-methylimidazolium chloride ionic liquid (AmimCl), 1-butyl-3-methylimidazolium chloride ionic liquid (BmimCl), 1-allyl-3-methylimidazolium chloride ionic liquid (AmimCl) / N,N-dimethylacetamide (DMAc) (the mass ratio of AmimCl to DMAc is 9:1), 1-ethyl-3- To a mixture of methylimidazole chloride ionic liquid (EmimCl) and 1-methylimidazole (Mim) (EmimCl to Mim mass ratio of 8:2), a certain amount of 2-methylbenzoyl chloride and a catalytic amount of pyridine are added. The mass ratio of cellulose to 2-methylbenzoyl chloride can be 1:5, 1:6, or 1:7. The reaction is carried out at 80°C for 2 hours. After completion, the precipitate is poured into methanol and washed 6-8 times with a solution of water, ethanol, DMF, or aqueous NaOH to remove residual impurities. The washed cellulose 2-methylbenzoate gel is dispersed in pure water at a mass ratio of 9:1. The gel is then crushed and pulverized using a colloid mill or high-pressure homogenizer to a particle size of 1-50 μm. The cellulose 2-methylbenzoate matrix gel is then sterilized by autoclaving.

[0120] 7) Preparation of Cellulose Acetate 2-Methylbenzoate Mixed Ester Matrix Gel

[0121] Weigh 8g of cellulose. The cellulose that can be used includes microcrystalline cellulose, wood pulp, and cotton pulp, and dissolve it in 92g of ionic liquid. The ionic liquid can be 1-allyl-3-methylimidazolium chloride ionic liquid (AmimCl), 1-butyl-3-methylimidazolium chloride ionic liquid (BmimCl), 1-allyl-3-methylimidazolium chloride ionic liquid (AmimCl) / N,N-dimethylacetamide (DMAc) (the mass ratio of AmimCl to DMAc is 9:1), 1-ethyl-3-methylimidazolium chloride ionic liquid (EmimCl) / 1-methylimidazole (Mim) (the mass ratio of EmimCl to Mim is 8:2), add 42.94g 2-Methylbenzoyl chloride and a catalytic amount of pyridine (the mass ratio of the raw material to 2-methylbenzoyl chloride can be 1:5, 1:6, 1:7, etc.) are reacted at 80°C for 2 hours. 4.85g of acetyl chloride is then added and the reaction is continued at 80°C for 2 hours. After the reaction, the product is poured into methanol to precipitate. The product is washed 6-8 times with a solution such as water, ethanol, DMF, or aqueous NaOH to remove residual impurities. The washed cellulose acetate 2-methylbenzoate mixed ester gel is dispersed in pure water at a mass ratio of 9:1. The gel is then crushed using a colloid mill, high-pressure homogenizer, or the like to a particle size of 1-50μm. The resulting cellulose acetate 2-methylbenzoate mixed ester matrix gel is then sterilized by autoclaving.

[0122] 8) Preparation of cellulose 2-methylbenzoate-4-trifluoromethylbenzoate mixed ester matrix glue

[0123] Weigh 8g of cellulose and dissolve it in 92g of ionic liquid. The cellulose that can be used includes microcrystalline cellulose, wood pulp, and cotton pulp. The ionic liquid can be 1-allyl-3-methylimidazolium chloride ionic liquid (AmimCl), 1-butyl-3-methylimidazolium chloride ionic liquid (BmimCl), 1-allyl-3-methylimidazolium chloride ionic liquid (AmimCl) / N,N-dimethylacetamide (DMAc) (the mass ratio of AmimCl to DMAc is 9:1), 1-ethyl-3-methylimidazolium chloride ionic liquid (EmimCl) / 1-methylimidazole (Mim) (the mass ratio of EmimCl to Mim is 8:2), add 42.94g 2-Methylbenzoyl chloride and a catalytic amount of pyridine are prepared in a mass ratio of 1:5, 1:6, or 1:7. The reaction is carried out at 80°C for 2 hours. 4.85 g of 4-trifluoromethylbenzoyl chloride is then added and the reaction is continued at 80°C for another 2 hours. After the reaction is completed, the mixture is poured into methanol for precipitation. The product is washed 6-8 times with a solution such as water, ethanol, DMF, or aqueous NaOH to remove residual impurities. The washed cellulose 2-methylbenzoate-4-trifluoromethylbenzoate mixed ester gel is dispersed in pure water at a mass ratio of 9:1 to water. The gel is then crushed using a colloid mill, high-pressure homogenizer, or the like to a particle size of 1-50 μm. The mixture is then sterilized by autoclaving to obtain a cellulose 2-methylbenzoate-4-trifluoromethylbenzoate mixed ester matrix gel.

[0124] 9) Preparation of Cellulose Acetate and Adamantane Carboxylate Mixed Ester Matrix Gel

[0125] Add 20g of cellulose to 480g of an ionic liquid and mechanically stir at 80°C for 2 hours to dissolve the cellulose. The cellulose can be microcrystalline cellulose, refined cotton, cotton pulp, or wood pulp. The ionic liquid can be one of allylmethylimidazole chloride, butylmethylimidazole acetate, or ethylmethylimidazole chloride. Add 34g of pyridine as a cosolvent and stir for 5 minutes. The molar ratio of pyridine to the anhydroglucose units in the cellulose is 3.5:1. Add acetic anhydride and adamantanecarbonyl chloride simultaneously and mechanically stir for 2 hours, maintaining the temperature at 80°C. The molar ratio of adamantanecarbonyl chloride to acetic anhydride to the anhydroglucose units in the cellulose can be 1:1, 2:1, 3:1, or 4:1. After the reaction is complete, pour the reaction solution into a coagulation bath to precipitate the product, which is then purified with DMSO. Wash the gel 6-8 times with a solution such as water, ethanol, acetone, or DMF to remove any residual DMSO. The washed cellulose acetate adamantane carboxylate mixed ester gel is dispersed in pure water with a mass ratio of water to cellulose acetate adamantane carboxylate mixed ester gel of 9:1. The gel is then crushed and pulverized using a colloid mill, a high-pressure homogenizer, or the like to a particle size of 1-50 μm and a solid content of 0.1-3.0 wt%. After high-pressure sterilization, the cellulose acetate adamantane carboxylate mixed ester matrix gel is obtained.

[0126] (3) Preparation of oxidized cellulose-dialdehyde cellulose matrix glue

[0127] Weigh 30g of cellulose and add it to 570g of ionic liquid. Mechanically stir at 80°C for 2h to dissolve the cellulose. The cellulose can be microcrystalline cellulose, refined cotton, cotton pulp, or wood pulp. The ionic liquid can be one of allylmethylimidazole chloride ionic liquid, butylmethylimidazole acetate ionic liquid, and ethylmethylimidazole chloride ionic liquid. After the reaction flask is tightly covered with tin foil to avoid light, a certain amount of sodium periodate is added and the reaction is stirred at 80°C for 10 hours. The molar ratio of sodium periodate to cellulose can be 0.02: 1, 0.05: 1, 0.1: 1, or 0.2: 1. After the reaction is completed, deionized water is added for precipitation and washing, and the crude product is filtered to obtain the crude product. The product is washed 6-8 times with a solution to remove residual impurities. The solution that can be used is water, ethanol, acetone, or ethylene glycol. The washed dialdehyde cellulose gel is dispersed in pure water with a mass ratio of water to dialdehyde cellulose gel of 9:1. The gel is then crushed and pulverized using a colloid mill, a high-pressure homogenizer, or the like to a particle size of 1-50 μm and a solid content of 0.1-3.0 wt%. The dialdehyde cellulose matrix glue is obtained after high-pressure sterilization.

[0128] (4) Preparation of DOPO (9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide) cellulose derivative matrix glue

[0129] 1) Preparation of Cellulose Acrylate: 10 g of cellulose was added to 190 g of the ionic liquid 1-allyl-3-methylimidazolium chloride (AmimCl) and mechanically stirred at 80°C for 2 hours to dissolve the cellulose. The cellulose could be microcrystalline cellulose, refined cotton, cotton pulp, or wood pulp. The cellulose solution was placed in a 50°C oil bath and allowed to stabilize for half an hour. Then, 2.8 g of acryloyl chloride was added and mechanically stirred at 300 rpm for 2 hours. After the reaction, the intermediate product, cellulose acrylate, was obtained by precipitation, washing, and drying.

[0130] 2) Preparation of DOPO-type cellulose derivative matrix glue: A certain amount of DOPO is dissolved in DMSO to prepare a 10% by weight solution. A base is added as a catalyst. 10 g of cellulose acrylate from step (1) is dissolved in 190 g of DMSO and slowly added dropwise to the DOPO solution. The mixture is reacted at 80°C for 12 hours. The molar ratio of DOPO to cellulose can be 1:1, 2:1, 3:1, or 4:1. The base can be sodium carbonate, triethylamine, sodium borohydride, or sodium hydride. The reaction solution is poured into methanol for precipitation. The product is washed 6-8 times with a solution such as water, ethanol, acetone, or ethylene glycol to remove residual impurities. The washed DOPO-type cellulose derivative gel is dispersed in pure water at a water to DOPO-type cellulose derivative gel mass ratio of 9:1. The gel is then crushed and pulverized using a colloid mill, high-pressure homogenizer, or the like to a particle size of 1-50 μm and a solid content of 0.1-3.0 wt%. The DOPO-type cellulose derivative matrix glue is obtained after autoclaving.

[0131] 2. Construction of CDX Xenograft Model:

[0132] (1) Method for establishing CDX xenograft model

[0133] 1. Select cells that are in good growth condition and exhibiting logarithmic growth. The recommended inoculation dose is: 5×10^6 cells / 100μl / cell and 100μl of Matrigel / cell, i.e., the ratio of cell suspension to Matrigel is 1:1.

[0134] 2. Mix the matrix gel and cell suspension at a ratio of 1:1.

[0135] 3. Use a syringe and needle to draw up the matrix gel cell suspension to be inoculated.

[0136] 4. Inoculation: 200 μl / mouse.

[0137] (II) CDX xenograft model

[0138] 1. Construction of a tumorigenic model of HCT116 subcutaneously transplanted into nude mice using methylcellulose matrix gel MC-1 of the present invention

[0139] BALB / c-Nude mice were subcutaneously inoculated with HCT116-Luc cells. HCT116-Luc cells were cultured and recovered, and the number of recovered progeny was recorded. HCT116-Luc cells were harvested during the logarithmic growth phase, the culture medium was removed, and cells were washed with DPBS before inoculation (cell survival was measured before and after tumor inoculation). The inoculation volume was 5×106 / mouse / 100 μL / mouse (with Matrigel in a 1:1 ratio) and the inoculation site was the right hind limb.

[0140] The formula for calculating tumor volume is: tumor volume (mm 3 ) = 0.5 × tumor long diameter × tumor short diameter 2 .

[0141] 2. Construction of a tumorigenic model of HCT116 subcutaneously transplanted into nude mice using animal-derived matrix gel (Corning, 356234)

[0142] The specific method for model construction is the same as the method for constructing a tumorigenic model of HCT116 subcutaneously transplanted into nude mice using methylcellulose matrix gel MC-1 of the present invention, with the only difference being that the matrix gel used in this part is a known animal-derived matrix gel (Corning, 356234) instead of the methylcellulose MC-1 matrix gel of the present invention.

[0143] Table 1 Comparative effects of constructing CDX xenograft models using methylcellulose matrix glue MC-1 and animal-derived matrix glue (Corning, 356234)

[0144]

[0145] The results in Table 1 show that compared with traditional animal-derived matrix gel, the methylcellulose MC-1 matrix gel of the present invention forms tumors faster and has a larger volume.

[0146] 3. Construction of PDX Xenograft Models:

[0147] (1) PDX xenograft model construction method

[0148] 1. Mouse preparation: Anesthetize and disinfect the mice according to experimental requirements.

[0149] 2. Preparation of the transplant site: Common transplant sites are subcutaneous or in situ (such as under the renal capsule). A small incision is made at the transplant site.

[0150] 3. Tumor tissue preparation: After receiving fresh tumor tissue, store it at 4°C for transportation and begin modeling within 2 hours. During modeling, remove any necrotic tumor tissue and cut the tumor into 3 x 3 x 3 mm pieces. Each piece should be embedded in Matrigel.

[0151] 4. Transplantation: Use sterile surgical instruments to implant the tumor tissue mixed with matrix gel into the transplantation site of the mouse. Ensure that the transplant is placed stably to avoid displacement or falling off.

[0152] 5. Postoperative monitoring: After the incision is sutured, the tumor formation of the animals is observed every day.

[0153] (II) PDX xenograft model

[0154] 1. Construction of a tumorigenic model of NCG mice subcutaneously inoculated with lung cancer using the oxidized cellulose-dialdehyde cellulose matrix gel of the present invention

[0155] Fresh tumor tissue was cleaned of necrotic parts and cut into small pieces of 3*3*3mm. The small pieces of tissue were then placed in biomass-based hydrogel. The NCG mice were anesthetized and disinfected. A small incision was made subcutaneously in the upper limbs. A small piece of tissue was transplanted into each mouse. The incision was sutured and the tumor formation was observed every day.

[0156] The formula for calculating tumor volume is: tumor volume (mm 3 ) = 0.5 × tumor long diameter × tumor short diameter 2 .

[0157] 2. Construction of a tumorigenic model of NCG mice subcutaneously inoculated with animal-derived matrix gel (Corning, 356234) for lung cancer

[0158] The specific method for model construction is the same as the method for constructing a tumorigenic model of NCG mice subcutaneously inoculated with lung cancer using oxidized cellulose-dialdehyde cellulose matrix glue of the present invention. The only difference is that the matrix glue in this part uses the known animal-derived matrix glue (Corning, 356234) instead of the oxidized cellulose-dialdehyde cellulose matrix glue of the present invention.

[0159] Table 2 Comparative effects of using oxidized cellulose-dialdehyde cellulose matrigel and animal-derived matrigel (Corning, 356234) to construct PDX xenograft models

[0160]

[0161] The results in Table 2 show that compared with traditional animal-derived matrix gel, oxidized cellulose-dialdehyde cellulose matrix gel forms tumors faster and has a larger volume.

[0162] The above describes the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the scope of protection of the present invention.

Claims

1. A cellulose derivative matrix glue, characterized in that The matrix of the cellulose derivative matrix glue is a cellulose derivative. The cellulose derivative matrix glue is composed of ultrafine fibers and has a network structure and a highly ordered three-dimensional micro-nano structure.

2. The cellulose derivative matrix glue according to claim 1, characterized in that The cellulose derivatives include cellulose esters, cellulose ethers, oxidized cellulose, charged cellulose or other types of cellulose derivatives; Preferably, the cellulose ester comprises cellulose monoester or cellulose mixed ester; Preferably, the cellulose monoester comprises cellulose organic acid ester or cellulose inorganic acid ester; Preferably, the cellulose organic acid ester includes cellulose methyl ester, cellulose ethyl ester, cellulose propyl ester, cellulose butyl ester, cellulose octadecyl ester and other saturated and unsaturated fatty acid esters, cellulose benzoate and other aromatic esters; cellulose lactate, cellulose citrate, cellulose carbamate, cellulose cyclohexylcarboxylate, cellulose cinnamate or cellulose 2-methylbenzoate, etc.; Preferably, the cellulose inorganic acid ester includes cellulose phosphate, cellulose sulfate or cellulose nitrate; Preferably, the cellulose mixed ester includes cellulose acetate butyrate CAB, cellulose acetate propionate CAP, cellulose acetate 2-methylbenzoate mixed ester, cellulose 2-methylbenzoate-4-trifluoromethylbenzoate mixed ester or cellulose acetate adamantane carboxylate mixed ester, etc. Preferably, the cellulose ether comprises cellulose monoether or cellulose mixed ether; Preferably, the cellulose ether includes methyl cellulose MC, ethyl cellulose AC, propyl cellulose PC or carboxymethyl cellulose CMC; Preferably, the cellulose mixed ether includes hydroxymethyl cellulose HMC, hydroxypropyl cellulose HPC or hydroxypropyl methyl cellulose HPMC; Preferably, the oxidized cellulose includes dialdehyde cellulose, glycol cellulose, dicarboxyl cellulose, etc.; Preferably, the charged cellulose comprises cationic cellulose or anionic cellulose and salts thereof; Preferably, the cationic cellulose includes a quaternary ammonium group, an imidazole group or a pyridyl group; Preferably, the anionic cellulose and salts include those containing carboxyl, hydroxide, sulfate or phosphate groups; Preferably, other cellulose derivatives include cellulose containing a DOPO structure, alkylated cellulose, aminated cellulose, chlorinated cellulose, amidated cellulose, silanized cellulose or plasma-modified cellulose.

3. The cellulose derivative matrix glue according to claim 1 or 2, characterized in that The fiber diameter of the cellulose derivative is 0.01 μm to 0.10 μm, for example, 0.01 μm, 0.02 μm, 0.03 μm, 0.04 μm, 0.05 μm, 0.06 μm, 0.07 μm, 0.08 μm, 0.09 μm or 0.10 μm. Preferably, the particle size of the matrix in the matrigel is 1 μm-50 μm, for example, 1 μm, 5 μm, 8 μm, 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 35 μm, 40 μm, 45 μm or 50 μm.

4. A method for preparing the cellulose derivative matrix glue according to any one of claims 1 to 3, wherein the method is selected from the following scheme 1 or scheme 2: Option 1: 1) Cellulose pretreatment; 2) homogeneously or heterogeneously derivatizing cellulose to obtain cellulose derivatives; 3) preparing the cellulose derivative in step 2) into a solution and pouring it into a coagulation bath to form a cellulose derivative matrix glue, in, In step 1), the cellulose pretreatment comprises dispersing the cellulose in a solvent, which may be water, DMF, ethanol or isopropanol, and the cellulose may be microcrystalline cellulose, cotton pulp, wood pulp, inulin, soluble starch or dextran, preferably wood pulp; or the cellulose pretreatment comprises adding the cellulose to a cellulose solvent to form a cellulose solution; Preferably, step 1) further comprises adding a certain amount of alkali to activate the cellulose, and the alkali can be sodium hydroxide, potassium hydroxide, sodium carbonate or sodium borohydride; Preferably, in step 3), the solvent used to prepare the solution can be water, ethanol, acetone, DMF or NaOH aqueous solution; Option 2: 1) dissolving cellulose with a cellulose solvent; 2) pouring the cellulose solution obtained in step 1) into a coagulation bath to form a cellulose gel; 3) subjecting the cellulose gel of step 2) to a derivatization reaction to obtain a cellulose derivative matrix gel; Wherein, in step 1) of scheme 1 or scheme 2, the cellulose solvent is any good solvent known in the art that can dissolve cellulose (the dissolution includes complete dissolution and partial dissolution). Preferably, it can be selected from one or more of the following systems: copper ammonia solution, copper ethylenediamine solution, organic solvent, ionic liquid, mixed solvent of ionic liquid and organic solvent, choline-type ionic liquid deep eutectic solvent system, organic solvent / salt system, amine oxide system (NMMO), carbamate system, alkali / water system, alkali / urea system, alkali / thiourea system, liquid ammonia / NH4SCN, organic acid, metal salt aqueous solution, alcohol solution of metal salt hydrate, water-alcohol mixed solution of metal salt hydrate, and the like solvent system; The organic solvent may be selected from one or more of N,N-dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAc), N-methyl-2-pyrrolidone (NMP), N-methylimidazole, imidazole, pyridine, ethylenediamine, hexafluoroacetone, hexafluoroisopropanol, glycerol, methyl isobutyl ketone, tetrahydrofuran, dioxane, and γ-valerolactone (GVL); The organic solvent / salt system may be selected from one or more of N,N-dimethylacetamide / lithium chloride (DMAc / LiCl) system, N-methyl-2-pyrrolidone / NMP, and N,N-dimethyl sulfoxide / tetrabutylammonium fluoride system (DMSO / TBAF); Wherein, the alkali / water system can be selected from one or both of NaOH / H2O and KOH / H2O; Wherein, the alkali / urea system can be selected from NaOH / Urea; Wherein, the alkaline / thiourea system is selected from NaOH / thio-urea; The organic acid may be selected from one or more of formic acid, acetic acid, propionic acid, butyric acid, succinic acid, lactic acid, glutamic acid, glycine, dichloroacetic acid, trichloroacetic acid, and toluenesulfonic acid; Wherein, the metal salt aqueous solution is preferably selected from aqueous solutions of metal salts such as CaCl2, ZnCl2, LiClO4, Ca(SCN)2, and LiSCN; Wherein, the alcohol solution of the metal salt hydrate can be selected from a methanol solution of CaBr2·H2O and a methanol solution of CaCl2·2H2O; Wherein, the water-alcohol mixed solution of the metal salt hydrate can be selected from a methanol aqueous solution of CaBr2·H2O and a methanol aqueous solution of CaCl2·2H2O; Wherein, the amine oxide system can be NMMO / H2O / DMSO system, NMMO / H2O / diethyltriamine, NMMO / H2O system; Wherein, the ionic liquid is selected from an organic molten salt formed by cations and anions with a melting point below 100°C, preferably an organic molten salt that can dissolve the biomass natural polymer; For example, the cation of the ionic liquid is selected from one or more substituted or unsubstituted imidazole, pyridine, pyrrole, amine, phosphine, choline, diazabicyclic, amino acid type cations; for example, the substituent can be C 1-6 Alkyl, C 1-6 One or more of alkenyl, phenyl or substituted phenyl; preferably one or more of methyl, ethyl, butyl and allyl; Preferably, the cation is selected from one or more of the following cations: 1-ethyl-3-methylimidazolium cation ([EMIM]), 3-methylimidazolium cation ([MIM]), 1-propyl-3-methylimidazolium cation ([PMIM]), 1-allyl-3-methylimidazolium cation ([AMIM]), 1-butyl-3-methylimidazolium cation ([BMIM]), 1-butyl-2,3-dimethylimidazolium cation ([BMMIM]), 1,3-dimethylimidazolium cation ([MMIM]), 1-methoxyethyl-3-methylimidazolium cation ([MeOEMIM]), 1-methoxymethyl-3-methylimidazolium cation ([MeOMMIM]), 1-hydroxy-3-methylimidazolium cation ([HMIM]), 1-(2-hydroxyethyl)-3-methylimidazolium cation ([HOEMIM]), 1-methyl-3-benzylimidazolium cation ([MBzIM]), 1 cations such as 1-pentyl-3-methylimidazolium cation ([PeMIM]), 1-benzyl-3-methylimidazolium cation ([BzMIM]), 1-m-methoxybenzyl-3-methylimidazolium cation ([MeOBzMIM]), 1-m-methylbenzyl-3-methylimidazolium cation ([MeBzMIM]), N-methylpyridinium cation ([MPyr]), N-ethylpyridinium cation ([EPyr]), N-butylpyridinium cation ([BPyr]), N-n-hexylpyridinium cation ([HPyr]), 1-butyl-3-methylpyrrolidinium ion ([BMPyrr]), tris(2-hydroxyethyl)methylamine ([THEMA]), tetrabutylamine ([TBA]), tetrabutylphosphine ([PBu4]), glycine cation ([Gly]), choline cation ([Ch]), and 1,5-diazabicyclo[4.3.0]one-5-ene ([DBNH]); More preferably, the cation is selected from one or more of the following cations: 1-ethyl-3-methylimidazolium cation ([EMIM]), 1-allyl-3-methylimidazolium cation ([AMIM]), 1-butyl-3-methylimidazolium cation ([BMIM]), choline cation ([Ch]); For example, the anion is selected from one or more of halogen anions, organic acid radical ions, organic acid ester anions, amino acid type anions, etc.; Preferably, the anion is selected from one or more of the following anions: chloride ([Cl]), bromide ([Br]), fluoride ([F]), formate ([HCOO]), acetate ([CH3COO] or [Ac]), glycolate ([HOCH2COO]), propionate ([CH3CH2COO] or [OPr]), butyrate ([CH3CH2CH2COO] or [OBu]), octanoate ([Oct]), benzoate ([C6H5COO] or [PhCOO]), lactate ([CH3CH(OH)COO] or [Lac]), thioglycolate ([HSCH2COO]) , hexafluorophosphate ion ([PF6]), trifluoroborate ([BF3]), methyl phosphate ion ([(MeO)HPO2] or [MP]), dimethyl phosphate ion ([(MeO)2PO2] or [DMP]), diethyl phosphate ion ([(EtO)2PO2] or [DEP]), methyl sulfonate anion ([MeOSO3]), trifluoromethylsulfonate anion ([CF3SO3]), glycine anion ([Gly]), lysine anion ([Lys]), valine anion ([Val]), dicyanamide anion ([N(CN)2] or [DCA]), bistrifluoromethylsulfonimide ([Tf2N]), and the like; More preferably, the anion is selected from one or more of the following anions: chloride ion ([Cl]), formate ion ([HCOO]), acetate ion ([Ac]), methyl phosphate ion ([(MeO)HPO2] or [MP]), dimethyl phosphate ion ([(MeO)2PO2] or [DMP]) and dicyanamide anion ([N(CN)2] or [DCA]); Further preferably, the ionic liquid can be selected from one or more of the following ionic liquids: 1-ethyl-3-methylimidazolium chloride ionic liquid ([EMIM][Cl]), 1-ethyl-3-methylimidazolium bromide ionic liquid ([EMIM][Br]), 1-ethyl-3-methylimidazolium formate ionic liquid ([EMIM][HCOO]), 1-ethyl-3-methylimidazolium acetate ionic liquid ([EMIM][Ac]), 1-ethyl-3-methylimidazolium octanoate ionic liquid ([EMIM][Oct]), 1-ethyl-3-methylimidazolium methyl phosphate ionic liquid ([EMIM][MP]), 1-ethyl-3-methylimidazolium dimethyl phosphate ionic liquid ([EMIM][MP]), [EMIM][DMP]), 1-ethyl-3-methylimidazolium diethyl phosphate ionic liquid ([EMIM][DEP]), 1-ethyl-3-methylimidazolium propionate ionic liquid ([EMIM][OPr]), 1-ethyl-3-methylimidazolium top ionic liquid ([EMIM][OBu]), 1-ethyl-3-methylimidazolium glycinate ionic liquid ([EMIM][Gly]), 1-ethyl-3-methylimidazolium lysine ionic liquid ([EMIM][Lys]), 1-allyl-3-methylimidazolium chloride ionic liquid ([AMIM][Cl]), 1-allyl-3-methylimidazolium bromide ionic liquid ([AMIM][Br]), 1-ethyl-3-methylimidazolium octanoate ionic liquid ([EMIM][C1]), 1-ethyl-3-methylimidazolium lysine ionic liquid ([EMIM][C2]), 1-ethyl-3-methylimidazolium chloride ionic liquid ([AMIM][Cl]), 1-ethyl-3-methylimidazolium bromide ionic liquid ([AMIM][Br]), 1-ethyl-3-methylimidazolium octanoate ionic liquid ([EMIM][C3]), 1-ethyl-3-methylimidazolium chloride ionic liquid ([EMIM][C4]), 1-ethyl-3-methylimidazolium chloride ionic liquid ([EMIM][C5]), 1-ethyl-3-methylimidazolium chloride ionic liquid ([EMIM][C6]), 1-ethyl-3-methylimidazolium chloride ionic liquid ([EMIM][C7]), 1-ethyl-3-methylimidazolium chloride ionic liquid ([EMIM][C8]), 1-ethyl-3-methylimidazolium chloride ionic liquid ([EMIM][ Propyl-3-methylimidazolium formate ionic liquid ([AMIM][HCOO]), 1-allyl-3-methylimidazolium acetate ionic liquid ([AMIM][Ac]), 1-butyl-3-methylimidazolium chloride ionic liquid ([BMIM][Cl]), 1-butyl-3-methylimidazolium bromide ionic liquid ([BMIM][Br]), 1-butyl-3-methylimidazolium formate ionic liquid ([BMIM][HCOO]), 1-butyl-3-methylimidazolium acetate ionic liquid ([BMIM][Ac]), 1-butyl-3-methylimidazolium hydroxyacetate ionic liquid ([BMIM][HOCH2COO]), 1-butyl-3-methylimidazolium propionate ionic liquid 1-Butyl-3-methylimidazolium lactate ionic liquid [BMIM][Lac], 1-Butyl-3-methylimidazolium butyrate ionic liquid ([BMIM][CH3CH2CH2COO]), 1-Butyl-3-methylimidazolium benzoate ionic liquid ([BMIM][C6H5COO]), 1-Butyl-3-methylimidazolium glycinate ionic liquid ([BMIM][H2NCH2COO]), 1-Butyl-3-methylimidazolium dicyanamide ionic liquid ([BMIM][N(CN)2]), 1-Butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquid ([BMIM][Tf2N]),1-Butyl-3-methylimidazolium hexafluorophosphate ionic liquid ([BMIM][PF6]), 1-Butyl-3-methylimidazolium tetrafluoroborate ionic liquid ([BMIM][BF4]), 1-Butyl-3-methylimidazolium methanesulfonate ionic liquid ([BMIM][MeOSO3]), 1-Butyl-3-methylimidazolium trifluoromethylsulfonate ionic liquid ([BMIM][CF3SO3]), 1-Butyl-2,3-dimethylimidazolium tetrafluoroborate ionic liquid ([BMMIM][BF4]), 3-Methylimidazolium formate ionic liquid ([MIM][HCOO]), 1,3-Dimethylimidazolium chloride ionic liquid ([MMIM][Cl]), 1,3-Dimethyl 1-(2-hydroxyethyl)-3-methylimidazolium chloride ionic liquid ([HOEMIM][Cl]), 1-methoxymethyl-3-methylimidazolium bromide ionic liquid ([MeOMMIM][Br]), 1-methoxyethyl-3-methylimidazolium chloride ionic liquid ([HMIM][Cl]), 1-hydroxy-3-methylimidazolium trifluoromethylsulfonate ionic liquid ([HMIM][CF3SO3]), 1-(2-hydroxyethyl)-3-methylimidazolium chloride ionic liquid ([HOEMIM][Cl]), 1-methoxymethyl-3-methylimidazolium bromide ionic liquid ([MeOMMIM][Br]), 1-methoxyethyl-3-methylimidazolium chloride ionic liquid ([HMIM][Cl]), 1-methoxyethyl ...methoxyethyl-3-methylimidazolium chloride 3-Methylimidazolium bromide ionic liquid ([MeOEMIM][Br]), N-ethylpyridinium chloride ionic liquid ([EPyr][Cl]), N-ethylpyridinium bromide ionic liquid ([EPyr][Br]), N-methylpicolinate ionic liquid ([MPyr][HCOO]), tris(2-hydroxyethyl)methylamine acetate ionic liquid ([THEMA][Ac]), tris(2-hydroxyethyl)methylamine methanesulfonate ionic liquid ([THEMA][MeOSO3]), tris(2-hydroxyethyl)methylamine trifluoromethanesulfonate ionic liquid [THEMA][CF3SO3], tetrabutylphosphine valine ionic liquid [PBu4][Val], tetrabutylphosphine lysate Amine salt ionic liquid [PBu4][Lys], tetrabutylphosphine glycinate ionic liquid [PBu4][Gly], 1-benzyl-3-methylimidazolium chloride ionic liquid ([BzMIM][Cl]), 1-benzyl-3-methylimidazolium dicyanamide ionic liquid ([BzMIM][DCA]), 1-m-methylbenzyl-3-methylimidazolium chloride ionic liquid ([MeBzMIM][Cl]), 1-m-methoxybenzyl-3-methylimidazolium chloride ionic liquid ([MeOBzMIM][Cl]), choline chloride ionic liquid ([Ch][Cl]), choline bromide ionic liquid (Ch][Br]), choline acetate ionic liquid ([Ch][CH3COO]),Ionic liquids such as choline propionate ionic liquid ([Ch][CH3CH2COO]), choline butyrate ionic liquid ([Ch][CH3CH2CH2COO]), glycine hydrochloride ionic liquid ([Gly][Cl]), and 1,5-diazabicyclo[4.3.0]keto-5-ene acetate ionic liquid ([DBNH][Ac]); Preferably, the choline-type deep eutectic solvent system is selected from one or more of [Ch][Cl] / urea, [Ch][Br] / urea, [Ch][Cl] / thio-urea, [Ch][Cl] / glycerol, and [Ch][Cl] / lactic acid; Preferably, the solvent system for dissolving cellulose is selected from the ionic liquid and / or NaOH / Urea system; more preferably, the cellulose-dissolving ionic liquid is selected from one or more of [AMIM][Cl], [BMIM][Cl], [EMIM][Ac], and [BMIM][Ac].

5. The method according to claim 4, characterized in that The solid content of the cellulose derivative matrix glue is 0.1-3.0 wt %, for example, 0.1 wt %, 0.5 wt %, 1 wt %, 1.5 wt %, 2 wt %, 2.5 wt % or 3.0 wt %.

6. A method for constructing a tumor CDX or PDX model using the cellulose derivative matrix gel according to any one of claims 1 to 3.

7. A tumor CDX or PDX model obtained according to the method of claim 6.

8. Use of the tumor CDX or PDX model according to claim 7 in personalized precision diagnosis and treatment, preclinical drug screening of new anticancer drugs, and tumor disease research.

9. The method according to claim 6, the model according to claim 7 and the use according to claim 8, characterized in that The tumor is preferably a human gastric cancer tumor, a human intestinal cancer tumor, a human lung cancer tumor, a human pancreatic cancer tumor, a human breast cancer tumor or a human colon cancer tumor.

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