A MiR155 delivery system and its anti-tumor application

Abstract

The present invention provides a targeted MiR155 delivery system (MiR@PCPmP‑NPs). The present invention constructs a targeted MiR155 delivery system, which can simultaneously regulate TIDC and TAM, activate immune response and intervene in immunosuppressive microenvironment. After administration, the delivery system can reach tumor tissues through passive targeting, weak acid triggers PEG shedding and mannose exposure, promotes TIDC and TAM uptake and endocytosis, and realizes in vivo targeted nucleic acid delivery. MiR155 released from lysosomes acts on multiple targets in TIDC and TAM, activates immune response and intervenes in immunosuppressive microenvironment to inhibit tumor growth.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and in particular to a MiR155 delivery system and its anti-tumor application. Background Art

[0002] Malignant tumors are a type of disease that seriously endangers human health. According to statistics, there are about 1.6 million new cancer patients in my country each year, and about 1.3 million people die from tumors each year. Existing tumor treatment methods mainly include radiotherapy, chemotherapy, surgical therapy, targeted drug therapy, immunotherapy and cell therapy. Among many treatment methods, anticancer drugs are often used as the main or auxiliary treatment method. However, the anti-tumor effect of existing anticancer drugs is not ideal. The important reason is that the anticancer drugs have poor tumor vascular permeability and are difficult to be absorbed and taken up by tumor cells, which greatly limits the therapeutic effect of anticancer drugs.

[0003] MicroRNA-155 (miR-155) is a multifunctional miRNA molecule. Experimental evidence shows that miR-155 plays an important role in inflammation, immune response and tumorigenesis. Low tumor immunogenicity and immunosuppressive microenvironment are key factors affecting tumor immunotherapy. Studies have found that microRNA-155 (MiR-155) can activate tumor-infiltrating dendritic cells (TIDC), activate and recruit CD8+T cells to kill tumors. MiR155 can also regulate the phenotype and function of tumor-associated macrophages (TAMs), intervene in the immunosuppressive microenvironment, and reduce the inhibitory effect on effector cells such as CD8+T. Therefore, effective delivery of MiR155 to TIDC and TAM can achieve dual regulation to enhance the tumor-killing ability of CD8+T cells. Summary of the invention

[0004] The present invention provides a targeted MiR155 delivery system (MiR@PCPmP-NPs) for simultaneously regulating TIDCs and TAMs, activating immune responses and intervening in immunosuppressive microenvironment.

[0005] The technical solution of the present invention is as follows: The first aspect of the present invention provides a delivery carrier, wherein the nanomaterial of the delivery carrier is PEG-CDM-PEI(Man)-ox-PCL, and its structural formula is shown in Formula I:

[0006]

[0007] Preferably, m is 30-60, more preferably 45-50, further preferably 49.

[0008] Preferably, n is 40-80, more preferably 40-45, further preferably 41.

[0009] Preferably, y is 40-80, more preferably 40-50, further preferably 48.

[0010] Preferably, the molecular weight of the PEG is 1500-2500, more preferably 1800-2200, further preferably 2210.85.

[0011] Preferably, the molecular weight of the PEI is 1500-2500, more preferably 1800-2200, further preferably 1800.

[0012] Preferably, the molecular weight of the PCL is 1500-6000, more preferably 3000-5500, further preferably 4811.

[0013] On the other hand, the present invention provides a method for preparing the nanomaterial PEG-CDM-PEI(Man)-ox-PCL, comprising the following steps:

[0014] (1) Preparation of PEG-CDM: CDM and DMF were dissolved in DCM, and oxalyl chloride was added dropwise. The reaction was carried out at 0°C for 15 min, and then at room temperature for 1 h. TEA was used as a catalyst and PEG solution was added dropwise. The reaction was carried out at 0°C for 30 min, and then at room temperature for 3 h. The reaction was terminated by NH4CL. The organic phase was collected, dried, filtered, and precipitated with cold ether. The precipitate was collected and dried in vacuum for 24 h to obtain the product PEG-CDM.

[0015] (2) Preparation of PCL-ox: ε-caprolactone and tert-butyl N-(3-hydroxypropyl)carbamate were reacted at 180°C for 24 h with Sn(Oct)2 as catalyst. After cooling to room temperature, the product was dissolved in chloroform and precipitated with cold ether. The precipitate was collected and dried to obtain PCL-NHBoc. PCL-NHBoc was reacted with TFA under stirring in an ice bath for 6 h. Under ice bath conditions, a saturated solution of NaHCO3 was added dropwise to the reaction solution until there were no bubbles. The mixture was dried with anhydrous Na2SO4, filtered, precipitated with cold ether, centrifuged at low temperature, and the precipitate was collected and dried to obtain the product PCL-NH2. Oxalyl chloride was dissolved in DCM, and PCL-NH2 solution was added dropwise with stirring at low temperature to react for 4 h. The mixture was washed with HCl three times, dried with anhydrous Na2SO4, filtered, precipitated with cold ether, and dried in a vacuum to constant weight to obtain the product PCL-ox.

[0016] (3) Preparation of PEI-ox-PCL: PCL-ox and TEA were dissolved in DCM. After stirring at room temperature for 30 min, PEI was added dropwise and stirred for 24 h. The mixture was precipitated with cold ether and centrifuged at low temperature. The precipitate was collected and dried to obtain the product PEI-ox-PCL.

[0017] (4) Preparation of PEG-CDM-PEI-ox-PCL: PEG-CDM and PEI-ox-PCL were dissolved in DMF at 0°C, TEA was added dropwise, and stirred for 30 min. After the reaction was completed, stirring was continued for 12 h in the dark at room temperature. Finally, cold ether precipitate was collected by centrifugation and vacuum dried for 24 h to obtain the product PEG-CDM-PEI-ox-PCL.

[0018] (5) Preparation of PEG-CDM-PEI(Man)-ox-PCL: PEG-CDM-PEI-ox-PCL and MPITC were dissolved in DMF solution and reacted in an oil bath at 50°C for 8 h using TEA as a catalyst. After the reaction, the reactants were placed in a dialysis bag and dialyzed for 24 h. The dialyzed contents were lyophilized to obtain the product PEG-CDM-PEI(Man)-ox-PCL.

[0019] On the other hand, the present invention provides a nanocomposition, which includes a delivery carrier and an active substance, wherein the nanomaterial of the delivery carrier is PEG-CDM-PEI(Man)-ox-PCL, and the active substance includes miR-155 or CUR.

[0020] On the other hand, the present invention provides a method for preparing the nanocomposite, comprising the following steps: accurately weighing 10 mg of nanomaterial and dissolving it in acetonitrile, rotary evaporating to form a thin film, hydrating at 60°C, centrifuging for 10 minutes, and taking the supernatant to obtain blank nanoparticles PCPmP-NPs. Taking 47.41 μg and mixing with 10 μg of miRNA to incubate, MiR@PCPmP-NPs nanocomposite is obtained.

[0021] On the other hand, the nanocomposition provided by the present invention is used for preparing anti-tumor drugs, wherein the tumors include breast cancer, lung cancer, colorectal cancer or gastric cancer, and the nanocomposition can be prepared into a solid preparation, a liquid preparation or a semisolid preparation.

[0022] The above technical scheme of the present invention has the following beneficial effects: The present invention constructs a targeted MiR155 delivery system (MiR@PCPmP-NPs), which can simultaneously regulate TIDC and TAM, activate immune response and intervene in immunosuppressive microenvironment. After administration, the delivery system can reach tumor tissues through passive targeting, weak acid triggers PEG shedding and mannose exposure, promotes TIDC and TAM uptake and endocytosis, and realizes in vivo targeted nucleic acid delivery. MiR155 released from lysosomes acts on multiple targets in TIDC and TAM, activates immune response and intervenes in immunosuppressive microenvironment, thereby inhibiting tumor growth.

[0023] Related definitions

[0024] CDM: 2,5-dihydroxy-4-methyl-2,5-dioxo-3-furanpropionic acid

[0025] PEI: Polyethyleneimine

[0026] Man: Mannose

[0027] Ox: tert-butyl N-(3-hydroxypropyl)carbamate

[0028] PCL: Polycaprolactone

[0029] PDI: Polymer Dispersibility Index

[0030] CMC: Critical micelle concentration

[0031] MPITC: 4-isothiocyanatophenyl α-D-mannopyranoside

[0032] PCPmP-NPs: Polyethylene glycol-2,5-dihydroxy-4-methyl-2,5-dioxo-3-furanpropionic acid-polyethyleneimine-4-isothiocyanatophenyl α-D-pyranoside-polycaprolactone nanoparticles

[0033] HBSS: Hank's balanced salt solution

[0034] MiR@PCPmP-NPs:

[0035] CD11c+ magnetic beads: Pan DC MicroBeads mouse

[0036] MHCⅡ: major histocompatibility complex BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 .Synthesis route of PEG-CDM-PEI(Man)-ox-PCL

[0038] Figure 2 . In vitro characterization of MiR@PCPmP NPs. Particle size (A) and potential (B) changes under different conditions; (C) Particle size and potential changes under different N / P ratios; (D) Gel retardation experiment; (E and F) Electrophoresis and fluorescence methods to determine miRNA release under different conditions.

[0039] Figure 3 .In vitro evaluation of complex uptake and cytotoxicity. (AD) TIDC and TAM uptake under different conditions; (E) CLSM observation of TIDC and TAM uptake; (F and G) Cytotoxicity of different complexes.

[0040] Figure 4. In vitro regulation of TIDC and TAM. (A and B) Expression of CD86, CD80 and MHCII after incubation with MiR@PCPmP NPs; (C) Release levels of IL-10 and IL-12 after TAM treatment with the complex.

[0041] Figure 5 . Distribution in vivo. (A) Distribution of Cy5-MiR@PCPmP in vivo; (B) Tumor frozen sections and immunofluorescence staining.

[0042] Figure 6 .In vivo antitumor effect. (AC) Tumor growth curves, tumor weight and inhibition rate of different treatment groups; (D) Dosage regimen; (E) Tumor photos of different treatment groups; (F) HE, Ki67 and TUNEL staining; (G) Tumor lung metastasis and HE staining. DETAILED DESCRIPTION

[0043] The present invention is further described below in conjunction with specific embodiments so that those skilled in the art can better understand the present invention and implement it, but the embodiments are not intended to limit the present invention.

[0044] Example 1

[0045] 1. Preparation of PEG-CDM-PEI[man]-ox-PCL carrier material

[0046] The preparation route of PEG-CDM-PEI[man]-ox-PCL carrier material is as follows Figure 1 shown.

[0047] (1) After CDM and DMF were dissolved in DCM, oxalyl chloride was added dropwise, and the reaction was carried out at 0°C for 15 min, and the reaction was continued at room temperature for 1 h. With TEA as a catalyst, PEG solution was added dropwise. The reaction was carried out at 0°C for 30 min, and the reaction was continued at room temperature for 3 h. The reaction was terminated by NH4CL. The organic phase was collected, dried, filtered, and precipitated with cold ether. The precipitate was collected and dried in vacuum for 24 h to obtain the product PEG-CDM. 1 The structure of the synthesized material was confirmed by HNMR and other methods.

[0048] (2) ε-caprolactone and tert-butyl N-(3-hydroxypropyl)carbamate were reacted at 180°C for 24 h with Sn(Oct)2 as catalyst. After cooling to room temperature, the product was dissolved in chloroform and precipitated with cold ether. The precipitate was collected and dried to obtain PCL-NHBoc. PCL-NHBoc was reacted with TFA under stirring in an ice bath for 6 h. Under an ice bath, a saturated solution of NaHCO3 was added dropwise to the reaction solution until there were no bubbles. The reaction solution was dried with anhydrous Na2SO4, filtered, precipitated with cold ether, centrifuged at low temperature, and the precipitate was collected and dried to obtain the product PCL-NH2. 1Oxalyl chloride was dissolved in DCM, and PCL-NH2 solution was added dropwise under low temperature stirring, and the reaction was continued for 4 hours. The mixture was washed with HCl three times, dried over anhydrous Na2SO4, filtered, precipitated with cold ether, and dried in vacuum to constant weight to obtain the product PCL-ox. 1 The structure of the synthesized material was confirmed by H NMR.

[0049] (3) PCL-ox and TEA were dissolved in DCM, stirred at room temperature for 30 min, and then PEI was added dropwise. The mixture was stirred for 24 h, precipitated with cold ether, centrifuged at low temperature, and the precipitate was collected and dried to obtain the product PEI-ox-PCL. 1 The structure of the synthesized material was confirmed by H NMR.

[0050] (4) PEG-CDM and PEI-ox-PCL were dissolved in DMF at 0°C, TEA was added dropwise, and the mixture was stirred for 30 min. After the reaction was completed, the mixture was stirred for 12 h in the dark at room temperature. Finally, the mixture was precipitated with cold ether, collected by centrifugation, and dried in vacuum for 24 h to obtain the product PEG-CDM-PEI-ox-PCL. 1 The structure of the synthesized material was confirmed by H NMR.

[0051] (5) PEG-CDM-PEI-ox-PCL and MPITC were dissolved in DMF solution and reacted in an oil bath at 50°C for 8 h using TEA as a catalyst. After the reaction, the reactants were placed in a dialysis bag and dialyzed for 24 h. The dialyzed contents were lyophilized to obtain the product PEG-CDM-PEI(Man)-ox-PCL). 1 The structure of the synthesized material was confirmed by H NMR.

[0052] PEG-CDM-PEI(man)-ox-PCL carrier material 1 H NMR characterization results (δ, ppm, CDCl3): 4.06(t,-OCH2CH2CH2CH2CH2COO-in PCL), 2.31(t,-OCH2CH2CH2CH2CH2COO-in PCL), 1.65(m,-OCH2CH2CH2CH2CH2COO-in PCL),1.38(m,-OCH2CH2CH2CH2CH2COO-in PCL),2.6-2.8(m,32H,H2NCH2CH2N-PEI),3.64(s,-CH2CH2-O-in PEG),2.29(t,=C(CH3)-in CDM),3.4(m,-C(S)NH-in MPTIC), molecular weight 8995.

[0053] Example 2 Preparation of MiR@PCPmP-NPs Nanocomposite

[0054] Accurately weigh 10 mg of nanomaterial and dissolve it in acetonitrile, rotary evaporate to form a thin film, hydrate at 60°C, centrifuge for 10 min, take the supernatant to obtain blank nanoparticles PCPmP-NPs, take 47.41 μg of blank nanoparticles and mix them with 10 μg of miRNA to obtain MiR@PCPmP-NPs nanocomposite.

[0055] Example 3 Optimization of preparation process of MiR@PCPmP-NPs nanocomposite

[0056] (1) Pharmaceutical optimization: Taking drug loading, encapsulation efficiency and particle size as indicators, the preparation method and process of nanoparticles were investigated to screen out the optimal formulation. The encapsulation efficiency of the micelle complex for Mir-155 was determined by ultrafiltration centrifugation, and the drug loading, encapsulation efficiency and release behavior were determined by fluorescence spectroscopy.

[0057] (2) Cell biology optimization: Based on the main biological indicators such as cytotoxicity, targeting, and cell uptake, the block composition and ratio, charge ratio, etc. of the complex are examined, and experiments are designed to determine the optimal composition.

[0058] like Figure 2 As shown in the figure, Zetasizer Nano measured the particle size of MiR@PCPmP NPs to be 182.2nm and the potential to be +23.5mV. Compared with blank nanoparticles, the particle size was significantly increased and the potential was significantly reduced. At the same time, the incubation results under different pH and redox conditions showed that low pH can promote PEG detachment, while 1mM H2O2 can significantly destroy the carrier structure, which is conducive to the release of miRNA.

[0059] Example 4 In vitro cytological evaluation of MiR / PCPmP-NPs complex

[0060] (1) Establishment of orthotopic breast cancer animal model: After female Balb / c mice were anesthetized, 5×10 5 4T1 cells were inoculated into the mouse mammary pad and then pressed. After 1-2 weeks, an orthotopic breast cancer tumor transplantation model was obtained.

[0061] (2) TIDC isolation and extraction: After the mice were killed by cervical dislocation, the tumor tissue was isolated in a sterile environment and cut into 8 mm 3 The cell suspension was collected, centrifuged and the supernatant was discarded. HBSS was added and washed twice by centrifugation. 2×10 7 The cells were inoculated into 6-well plates at a density of 10 cells / well and incubated for 4 h. The adherent cells were collected and TIDCs were sorted by CD11c+ magnetic beads, and the purity was greater than 90%.

[0062] (3) Cytotoxicity: TIDCs were seeded at a density of 10,000 cells / well in a 96-well plate and incubated overnight. A series of concentrations of complexes were added and incubated for 24 h and 48 h. After adding 20 μL of MTT solution and continuing to incubate for 4 h, 150 μL of DMSO was used to dissolve formazan and the absorbance was measured using a microplate reader (λ = 570 nm). Cell survival rate was calculated as follows: Cell survival rate (%) = (absorbance 处理 -Absorbance 空白 ) / (absorbance 对照 -Absorbance 空白 )×100%. The result is Figure 3 As shown, the prepared nanoparticles had less toxicity and higher survival rates of TIDCs and TAMs.

[0063] TAM isolation: Tumor volume was measured down to 1 cm after inoculation 3 , use sterilized surgical instruments to separate the tumor in a sterile environment and cut it into 2x2mm 3 The fragments were digested with 0.3% type IV collagenase and 0.05% DNase at 37°C for 40 min, the cell suspension was filtered with a 200-mesh sieve to remove incompletely digested tissue pieces, centrifuged at 1200 rpm, washed twice with HBSS balanced salt solution, added with red blood cell lysis buffer for 1-2 min, washed twice with HBSS balanced solution, centrifuged at 1200 rpm for 5 min, the precipitate was collected and dispersed in complete culture medium, the culture medium was replaced to remove non-adherent cells to obtain TAM with higher purity.

[0064] (4) Uptake and transport: Flow cytometry was used to investigate the uptake of the complex by TIDC. TIDC was placed at 1×10 6 cells / well were inoculated into 6-well plates and cultured overnight at 5% CO2 and 37°C. The complexes diluted in different pH culture medium were added and cultured for 4 hours. The cells were collected by trypsin digestion and washed before being tested. The uptake and transport of the fluorescently labeled complexes were observed using a laser confocal microscope. TIDCs were placed at 3×10 5 The cells / well density was inoculated in a 6-well plate with a slide, and cultured at 5% CO2 and 37°C for 24 hours. The diluted complex was added for co-incubation and observed by DAPI staining. Figure 4 As shown, weakly acidic conditions can significantly promote the uptake of nanocomplexes, and mannose modification can further improve the uptake efficiency. CLSM results show that miRNA can effectively escape from lysosomes and be released into the cytoplasm, which is conducive to its regulatory role.

[0065] (5) Expression of markers, genes and cytokines: TIDCs were inoculated in 6-well plates and cultured for 24 hours. The complex was added and cultured for another 48 hours. The supernatant was collected and the expression of IL-12 and other proteins was measured by ELISA. TIDCs were collected and evaluated by flow cytometry for their expression of CD80, CD86 and MHCⅡ. The results are shown in Figure 2. Figure 4 As shown in the figure, weakly acidic conditions can effectively promote the activation of TIDC and TAM, and upregulate CD80, CD86 and MHCII. At the same time, MiR@PCPmP NPs significantly inhibited IL-10 secretion and increased IL-12 release.

[0066] Example 5 In vivo evaluation of MiR / PCPmP-NPs complexes in tumor-bearing animals

[0067] (1) In vivo targeting: Fluorescently labeled MiR / PCPmP-NPs complexes were injected into the tail vein, and the dynamic distribution of Cy5.5-MiR155 in tumor-bearing mice was observed in real time using a small animal in vivo imaging device. Mice were killed by cervical dislocation, and various tissues and organs were collected and frozen sections were used to observe their uptake by TIDC in vivo. Figure 5 As shown in the figure, Cy5-MiR@PCPmP NPs can effectively accumulate in the tumor site, while other major organs are less distributed, indicating that the prepared carrier has good tumor targeting. The results of immunofluorescence sections show that Cy5-MiR@PCPmP NPs effectively target TIDC (CD11c+) and TAM (CD206+) in the tumor microenvironment, indicating its good cell targeting.

[0068] (2) Pharmacodynamics: Different dosing regimens were used to investigate the anti-tumor effects of the complex, such as tumor growth, weight change, and survival rate. Blood samples were collected to investigate the effect and interference of the carrier on the immune system. Mice were killed by cervical dislocation and tumors and various tissues were collected. Slices were made to observe the tumor inhibition effect and the effect on normal tissues and organs. Figure 6 As shown in the figure, MiR@PCPmP NPs can delay 4T1 tumor growth after tail vein injection, with the lowest tumor clock and the strongest inhibitory ability. The results of tumor sections showed that the MiR@PCPmP NPs group had the best tumor proliferation and apoptosis, and the lowest lung metastasis, indicating its good anti-tumor effect.

Claims

1. A delivery carrier PEG-CDM-PEI(Man)-ox-PCL having a structural formula as shown in Formula I, in, m is 45-50; n is 40-45; y is 40-50.

2. The delivery vector according to claim 1, characterized in that The molecular weight of the PEG is 1800-2200, and the molecular weight of the PEI is 1800-2200.

3. The delivery vector according to claim 1, characterized in that The molecular weight of the PCL is 3000-5500.

4. The method for preparing the nanomaterial PEG-CDM-PEI(Man)-ox-PCL according to claim 1, comprising the following steps: 1) Preparation of PEG-CDM: CDM and DMF were dissolved in DCM, and oxalyl chloride was added dropwise. The reaction was carried out at 0°C for 15 min and continued at room temperature for 1 h. TEA was used as a catalyst and PEG solution was added dropwise. The reaction was carried out at 0°C for 30 min and continued at room temperature for 3 h. The reaction was terminated by NH4CL. The organic phase was collected, dried, filtered, and precipitated with cold ether. The precipitate was collected and dried in vacuo for 24 h to obtain the product PEG-CDM. 2) Preparation of PCL-ox: ε-caprolactone and tert-butyl N-(3-hydroxypropyl)carbamate were reacted at 180°C for 24 h with Sn(Oct)2 as catalyst, and the reaction was carried out for 24 h at 180°C. The product was cooled to room temperature, and the product was dissolved in chloroform and precipitated with cold ether. The precipitate was collected and dried to obtain PCL-NHBoc. PCL-NHBoc and TFA were stirred and reacted for 6 h in an ice bath. A saturated solution of NaHCO3 was added dropwise to the reaction solution under ice bath conditions until there were no bubbles. The solution was dried with anhydrous Na2SO4 and filtered. The solution was precipitated with cold ether and centrifuged at low temperature. The precipitate was collected and dried to obtain the product PCL-NH2. Oxalyl chloride was dissolved in DCM, and PCL-NH2 solution was added dropwise with stirring at low temperature. The reaction was carried out for 4 h. The mixture was washed with HCl three times, dried with anhydrous Na2SO4 and filtered. The solution was precipitated with cold ether and dried in a vacuum to constant weight to obtain the product PCL-o. 3) Preparation of PEI-ox-PCL: PCL-ox and TEA were dissolved in DCM, stirred at room temperature for 30 min, PEI was added dropwise, stirred for 24 h, precipitated with cold ether, centrifuged at low temperature, and the precipitate was collected and dried to obtain the product PEI-ox-PCL; 4) Preparation of PEG-CDM-PEI-ox-PCL: PEG-CDM and PEI-ox-PCL were dissolved in DMF at 0°C, TEA was added dropwise, and stirred for 30 min. After the reaction was completed, stirring was continued for 12 h in the dark at room temperature, and finally cold ether was precipitated, collected by centrifugation, and vacuum dried for 24 h to obtain the product PEG-CDM-PEI-ox-PCL; 5) Preparation of PEG-CDM-PEI(Man)-ox-PCL: PEG-CDM-PEI-ox-PCL and MPITC were dissolved in DMF solution, and TEA was used as catalyst. The reaction was carried out in an oil bath at 50°C for 8 h. After the reaction, the reactants were placed in a dialysis bag for dialyzation for 24 h. The dialyzed contents were lyophilized to obtain the product PEG-CDM-PEI(Man)-ox-PCL.

5. A nanocomposition MiR@PCPmP-NPs, comprising the delivery vector according to claim 1 and an active substance, wherein the active substance comprises miR-155 or CUR.

6. The method for preparing the nanocomposite according to claim 5, comprising the following steps: Accurately weigh 10 mg of nanomaterial and dissolve it in acetonitrile, rotary evaporate to form a thin film, hydrate at 60°C, centrifuge for 10 min, take the supernatant to obtain blank nanoparticles PCPmP-NPs, take 47.41 μg of blank nanoparticles and mix them with 10 μg of miRNA to obtain MiR@PCPmP-NPs nanocomposite.

7. Use of the nanocomposition according to claim 5 for preparing anti-tumor drugs, wherein the tumor includes breast cancer, lung cancer, colorectal cancer or gastric cancer, and the nanocomposition can be prepared into a solid preparation, a liquid preparation or a semisolid preparation.

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