Bionanomaterial for treating retroperitoneal liposarcoma

Abstract

The invention relates to the field of biological materials, and particularly discloses a biological nanomaterial for treating retroperitoneal liposarcoma. The core layer, the middle layer and the shell layer are arranged to form the biological nano-material, the biological nano-material can accurately recognize tumor cells and stem cells, the targeting property of the medicine to the liposarcoma lipid microenvironment is enhanced, the shell layer can be dissolved in the in-vivo appropriate temperature and the tumor appropriate pH value environment, and the medicine can be used for treating liposarcoma. The functional component sequence in the middle layer is released, the therapeutic effect of the functional component is prolonged, and then the release effect of the loaded drug in the core layer is matched with the functional component in the middle layer, so that the drug resistance of tumor tissue cells to a single therapeutic drug is avoided, and the therapeutic effect of the biological nano material is improved.

Description

Technical Field

[0001] This invention belongs to the field of biomaterials technology, specifically relating to a bio-nanomaterial for the treatment of retroperitoneal liposarcoma. Background Technology

[0002] Retroperitoneal liposarcoma accounts for 10%–15% of soft tissue sarcomas. Due to its strong local invasiveness and proximity to major blood vessels, kidneys, and other vital organs, complete surgical resection is difficult, resulting in a five-year recurrence rate exceeding 70%. Current treatment methods have significant limitations: surgery is restricted by complex anatomy and often leaves microlesions; traditional chemotherapy drugs have a response rate of less than 25% to dedifferentiated subtypes, and the amount of traditional chemotherapy drugs that can reach the tumor area after intravenous injection is limited, resulting in low local drug concentrations and poor efficacy; targeted drugs are only effective for certain subtypes. Existing biomaterials also face multiple shortcomings: drug-loaded nanoparticles alone lack tumor tissue targeting; non-degradable scaffolds are prone to inducing chronic inflammatory responses.

[0003] As can be seen from the above, the existing systems are unable to specifically regulate the important root cause of recurrence—liposarcoma stem cells. Some existing therapeutic drugs lack targeting of the lipid microenvironment of liposarcoma, and single-drug therapy is difficult to overcome the drug resistance mechanism of tumor tissue cells, resulting in poor treatment effects. These factors together make retroperitoneal liposarcoma a thorny problem in clinical treatment. Summary of the Invention

[0004] In order to overcome the shortcomings of the prior art, the present invention aims to provide a bio-nanomaterial for the treatment of retroperitoneal liposarcoma, so as to solve the problem that the existing treatment methods lack targeting of the lipid microenvironment of liposarcoma and are difficult to overcome the drug resistance mechanism of tumor tissue cells, resulting in poor treatment effect.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] A biomaterial for the treatment of retroperitoneal liposarcoma comprises a core layer, an intermediate layer, and an outer shell. The core layer consists of a mesoporous silica nanoparticle carrier and a drug-loaded layer. The intermediate layer consists of a temperature-sensitive polymer and functional components. The outer shell consists of a hydrogel shell and additives.

[0007] Preferably, the loaded drug includes anlotinib, pebocillin, an MDM2 inhibitor, trabectedin, and siRNA.

[0008] Preferably, the surface of the mesoporous silica nanoparticle carrier is modified with folic acid and hyaluronic acid.

[0009] Preferably, the temperature-sensitive polymer is N-isopropylacrylamide-co-acrylic acid, and the functional components include PD-1 antibody covalent conjugate and interleukin-12 sustained-release microspheres.

[0010] Preferably, the hydrogel shell is a methacrylamide gelatin hydrogel, and the additives include platelet-derived growth factor and nano-hydroxyapatite.

[0011] Preferably, the additives further include polycaprolactone-polyethylene glycol-polycaprolactone, hyaluronic acid-polylysine grafts, and polyethylene glycol-polydopamine.

[0012] Preferably, the functional components further include a PI3K / mTOR dual-target inhibitor, liposome-encapsulated doxorubicin, and a β3-adrenergic receptor antagonist.

[0013] Preferably, the functional component further includes a matrix metalloproteinase-2 responsive peptide.

[0014] Preferably, the steps for preparing bio-nanomaterials include:

[0015] Mesoporous silica nanoparticle carriers were synthesized using the sol-gel method, and drugs were loaded into the mesoporous silica nanoparticle carriers by vacuum adsorption to form a core layer.

[0016] Temperature-sensitive polymers were synthesized on the surface of mesoporous silica nanoparticle carriers via RAFT polymerization, and functional components were embedded into the temperature-sensitive polymers to form an intermediate layer.

[0017] The intermediate layer particles were dispersed in an aqueous solution of methacryloyl gelatin, and after the addition of photoinitiators and additives, they were cured using ultraviolet light to form an outer shell layer, thus obtaining a bio-nanomaterial for the treatment of retroperitoneal liposarcoma.

[0018] Compared with the prior art, the beneficial effects of the present invention are:

[0019] This invention comprises a core layer, an intermediate layer, and an outer shell layer to form a bio-nanomaterial. This bio-nanomaterial can accurately identify tumor cells and stem cells, enhance the targeting of drugs to the lipid microenvironment of liposarcoma, and the outer shell layer can dissolve in the suitable temperature and pH environment of the tumor, releasing the functional component sequence in the intermediate layer and prolonging the therapeutic efficacy of the functional components. Subsequently, the drug-loaded release effect in the core layer works in conjunction with the functional components in the intermediate layer to avoid the development of drug resistance in tumor tissue cells to a single therapeutic drug. Moreover, this bio-nanomaterial can be precisely delivered to the tumor area, increasing the drug concentration in the local tumor area and improving the therapeutic effect of the bio-nanomaterial. Attached Figure Description

[0020] Figure 1This is a block diagram of the components of a bio-nanomaterial for the treatment of retroperitoneal liposarcoma disclosed in this invention;

[0021] Figure 2 This is a block diagram of a method for preparing bio-nanomaterials for the treatment of retroperitoneal liposarcoma disclosed in this invention. Detailed Implementation

[0022] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0023] Example 1:

[0024] Please see Figure 1 - Figure 2 As shown, a bio-nanomaterial for the treatment of retroperitoneal liposarcoma includes a core layer, an intermediate layer, and an outer shell. The core layer is composed of mesoporous silica nanoparticle carriers and drug loading, the intermediate layer is composed of temperature-sensitive polymers and functional components, and the outer shell is composed of a hydrogel shell and additives.

[0025] As can be seen from the above, by setting up a core layer, an intermediate layer and an outer shell to form a bio-nanomaterial, this bio-nanomaterial can accurately identify tumor cells and stem cells, enhance the targeting of drugs to the lipid microenvironment of liposarcoma, and the outer shell can dissolve in the suitable temperature and pH environment of the tumor, releasing the functional component sequence in the intermediate layer and prolonging the therapeutic effect of the functional components. Then, the drug release effect of the loaded core layer works in conjunction with the functional components in the intermediate layer to avoid the development of drug resistance in tumor tissue cells to a single therapeutic drug and improve the therapeutic effect of the bio-nanomaterial.

[0026] The loaded drugs include anlotinib, pebocilib, MDM2 inhibitors, trabectedin, and siRNA.

[0027] Anlotinib is a multi-target receptor tyrosine kinase inhibitor that inhibits tumor growth and metastasis by blocking tumor angiogenesis and cell proliferation pathways through the inhibition of targets such as vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), and platelet-derived growth factor receptors (PDGFRβ).137 It is mainly used to treat solid tumors such as non-small cell lung cancer, small cell lung cancer, soft tissue sarcoma, and medullary thyroid carcinoma, and has shown significant efficacy, especially in advanced patients who have failed previous chemotherapy.

[0028] Palbociclib is the world's first CDK4 / 6 inhibitor. It selectively inhibits cyclin-dependent kinase 4 / 6 (CDK4 / 6), blocking the cell cycle from the G1 phase to the S phase, thereby inhibiting tumor cell proliferation. It is mainly used in combination with endocrine drugs (such as letrozole or fulvestrant) to treat hormone receptor-positive (HR+), HER2-negative advanced breast cancer.

[0029] MDM2 is an E3 ubiquitin ligase containing a ring finger domain. The full-length human MD2 protein consists of 491 amino acids and has four functional domains involved in regulating cellular biological processes. In various subtypes of retroperitoneal liposarcoma, the MDM2 gene exhibits high copy number amplification, and its high expression is associated with poor prognosis. Clearly, the MDM2 gene plays a crucial role in retroperitoneal liposarcoma. Therefore, the MDM2 gene can be considered a therapeutic target for retroperitoneal liposarcoma, and its expression can be inhibited using MDM2 inhibitors such as RG7388 to prevent the formation of retroperitoneal liposarcoma.

[0030] The surface of the mesoporous silica nanoparticle carrier is modified with folic acid and hyaluronic acid to activate carboxyl groups via EDC / NHS.

[0031] The temperature-sensitive polymer is N-isopropylacrylamide-co-acrylic acid, and the reaction temperature is about 34°C, slightly lower than body temperature, to ensure that it can function under body temperature conditions. The functional components include PD-1 antibody covalent conjugate and interleukin-12 sustained-release microspheres. The PD-1 antibody covalent conjugate is directly coupled to the temperature-sensitive polymer, and the interleukin-12 sustained-release microspheres can be embedded in the temperature-sensitive polymer through an emulsification-crosslinking method.

[0032] The hydrogel shell is a methacrylamide gelatin hydrogel, and the additives include platelet-derived growth factor and nano-hydroxyapatite. The platelet-derived growth factor is distributed on the hydrogel shell and can mediate the binding of bio-nanomaterials with tumor cells, thereby improving the efficiency of bio-nanomaterials. Nano-hydroxyapatite can promote the repair of bone defects and prevent long-term bone defects at the sarcoma site.

[0033] When this bio-nanomaterial is applied, trabectedine is used to inhibit the oncogene FUS-CHOP formed by the fusion of the FUS and CHOP genes; siRNA is used to silence the MDM2 gene; PD-1 antibody is used to activate T cells; interleukin-12 can promote the secretion of IFN-γ, which has the function of inhibiting tumor cell proliferation. It is applied to the immunotherapy of malignant tumors by regulating the activity of the immune system; and methacryloyl gelatin is adhered to the wound and gradually degrades, matching the tissue regeneration at the wound site, ensuring continuous treatment while avoiding sarcoma recurrence and wound adhesion.

[0034] The steps for preparing bio-nanomaterials include:

[0035] Mesoporous silica nanoparticle carriers were synthesized using the sol-gel method, and drugs were loaded into the mesoporous silica nanoparticle carriers by vacuum adsorption to form a core layer.

[0036] Temperature-sensitive polymers were synthesized on the surface of mesoporous silica nanoparticle carriers via RAFT polymerization, and functional components were embedded into the temperature-sensitive polymers to form an intermediate layer.

[0037] The intermediate layer particles were dispersed in an aqueous solution of methacryloyl gelatin, and after the addition of photoinitiators and additives, they were cured using ultraviolet light to form an outer shell layer, thus obtaining a bio-nanomaterial for the treatment of retroperitoneal liposarcoma.

[0038] Example 2:

[0039] Please see Figure 1 - Figure 2 As shown, a bio-nanomaterial for the treatment of retroperitoneal liposarcoma includes a core layer, an intermediate layer, and an outer shell. The core layer is composed of mesoporous silica nanoparticle carriers and drug loading, the intermediate layer is composed of temperature-sensitive polymers and functional components, and the outer shell is composed of a hydrogel shell and additives.

[0040] As can be seen from the above, by setting up a core layer, an intermediate layer and an outer shell to form a bio-nanomaterial, this bio-nanomaterial can accurately identify tumor cells and stem cells, enhance the targeting of drugs to the lipid microenvironment of liposarcoma, and the outer shell can dissolve in the suitable temperature and pH environment of the tumor, releasing the functional component sequence in the intermediate layer and prolonging the therapeutic effect of the functional components. Then, the drug release effect of the loaded core layer works in conjunction with the functional components in the intermediate layer to avoid the development of drug resistance in tumor tissue cells to a single therapeutic drug and improve the therapeutic effect of the bio-nanomaterial.

[0041] The loaded drugs include anlotinib, pebocilib, MDM2 inhibitors, trabectedin, and siRNA.

[0042] Anlotinib is a multi-target receptor tyrosine kinase inhibitor that inhibits tumor growth and metastasis by blocking tumor angiogenesis and cell proliferation pathways through the inhibition of targets such as vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), and platelet-derived growth factor receptors (PDGFRβ).137 It is mainly used to treat solid tumors such as non-small cell lung cancer, small cell lung cancer, soft tissue sarcoma, and medullary thyroid carcinoma, and has shown significant efficacy, especially in advanced patients who have failed previous chemotherapy.

[0043] Palbociclib is the world's first CDK4 / 6 inhibitor. It selectively inhibits cyclin-dependent kinase 4 / 6 (CDK4 / 6), blocking the cell cycle from the G1 phase to the S phase, thereby inhibiting tumor cell proliferation. It is mainly used in combination with endocrine drugs (such as letrozole or fulvestrant) to treat hormone receptor-positive (HR+), HER2-negative advanced breast cancer.

[0044] MDM2 is an E3 ubiquitin ligase containing a ring finger domain. The full-length human MD2 protein consists of 491 amino acids and has four functional domains involved in regulating cellular biological processes. In various subtypes of retroperitoneal liposarcoma, the MDM2 gene exhibits high copy number amplification, and its high expression is associated with poor prognosis. Clearly, the MDM2 gene plays a crucial role in retroperitoneal liposarcoma. Therefore, the MDM2 gene can be considered a therapeutic target for retroperitoneal liposarcoma, and its expression can be inhibited using MDM2 inhibitors such as RG7388 to prevent the formation of retroperitoneal liposarcoma.

[0045] The surface of the mesoporous silica nanoparticle carrier is modified with folic acid and hyaluronic acid to activate carboxyl groups via EDC / NHS.

[0046] The temperature-sensitive polymer is N-isopropylacrylamide-co-acrylic acid, and the reaction temperature is about 34°C, slightly lower than body temperature, to ensure that it can function under body temperature conditions. The functional components include PD-1 antibody covalent conjugate and interleukin-12 sustained-release microspheres. The PD-1 antibody covalent conjugate is directly coupled to the temperature-sensitive polymer, and the interleukin-12 sustained-release microspheres can be embedded in the temperature-sensitive polymer through an emulsification-crosslinking method.

[0047] The hydrogel shell is a methacrylamide gelatin hydrogel, and the additives include platelet-derived growth factor and nano-hydroxyapatite. The platelet-derived growth factor is distributed on the hydrogel shell and can mediate the binding of bio-nanomaterials with tumor cells, thereby improving the efficiency of bio-nanomaterials. Nano-hydroxyapatite can promote the repair of bone defects and prevent long-term bone defects at the sarcoma site.

[0048] When this bio-nanomaterial is applied, trabectedine is used to inhibit the oncogene FUS-CHOP formed by the fusion of the FUS and CHOP genes; siRNA is used to silence the MDM2 gene; PD-1 antibody is used to activate T cells; interleukin-12 can promote the secretion of IFN-γ, which has the function of inhibiting tumor cell proliferation. It is applied to the immunotherapy of malignant tumors by regulating the activity of the immune system; and methacryloyl gelatin is adhered to the wound and gradually degrades, matching the tissue regeneration at the wound site, ensuring continuous treatment while avoiding sarcoma recurrence and wound adhesion.

[0049] The additives also include polycaprolactone-polyethylene glycol-polycaprolactone, hyaluronic acid-polylysine grafts, and polyethylene glycol-polydopamine. Polycaprolactone-polyethylene glycol-polycaprolactone is a triblock copolymer with lipid affinity, which promotes the penetration of nanoparticles into the adipose matrix. Hyaluronic acid-polylysine grafts, as a target for the CD44 receptor highly expressed in liposarcoma cells, enhance active targeting. Polyethylene glycol-polydopamine endows the material with pH responsiveness and photothermal conversion capabilities, enabling the nanomaterials to disassemble and reassemble in the acidic tumor microenvironment.

[0050] The functional components also include a PI3K / mTOR dual-target inhibitor, liposome-encapsulated doxorubicin, and a β3-adrenergic receptor antagonist. The PI3K / mTOR dual-target inhibitor can inhibit the abnormally activated PI3K pathway in liposarcoma cells, the liposome-encapsulated doxorubicin can reverse drug efflux mediated by the multidrug resistance protein ABCB1, and the β3-adrenergic receptor antagonist can block the release of free fatty acids from adipocytes into the tumor microenvironment and inhibit tumor energy supply.

[0051] The functional components also include matrix metalloproteinase-2 responsive peptides, which are degraded at the forefront of tumor invasion and enhance deep penetration.

[0052] To prepare polycaprolactone-polyethylene glycol-polycaprolactone, ε-caprolactone (10 mmol) and PEG (molecular weight 2000, 2 mmol) were polymerized at 120 °C for 6 hours under the catalysis of stannous octoate to obtain a triblock copolymer with a molecular weight of 5000-8000, which was then purified by dialysis and freeze-dried.

[0053] A targeting carrier composed of polycaprolactone-polyethylene glycol-polycaprolactone, hyaluronic acid-polylysine graft polymer, and polyethylene glycol-polydopamine was prepared. 100 mg of polycaprolactone-polyethylene glycol-polycaprolactone was dissolved in dichloromethane, and 30 mg of hyaluronic acid-polylysine graft polymer and 15 mg of polyethylene glycol-polydopamine were added to form the targeting carrier. The mixture was ultrasonically emulsified to form an oil phase. The aqueous phase was a PBS solution containing 10 mg of iron oxide nanoparticles at pH 7.4. The oil phase was added dropwise to the aqueous phase, and the mixture was ultrasonically run for 3 seconds with a 300W probe and paused for 2 seconds for a total of 5 minutes to form a primary emulsion. The organic solvent was removed by rotary evaporation to obtain a blank nanocarrier with a particle size of approximately 150 nm, which was stored at 4 °C.

[0054] 20 mg of PI 3K / mTOR dual-target inhibitor and 30 mg of liposome-encapsulated doxorubicin were dissolved in ethanol and loaded into a blank nanocarrier by thin-film dispersion, achieving an encapsulation efficiency of over 85%.

[0055] The matrix metalloproteinase-2 responsive peptide was linked to the end of a hyaluronic acid-polylysine graft via an amide bond, and then modified onto the surface of a nanocarrier through electrostatic interaction to form a targeting shell, thus obtaining core targeted drug nanoparticles.

[0056] The steps for preparing bio-nanomaterials include:

[0057] Mesoporous silica nanoparticle carriers were synthesized using the sol-gel method. Drug-loaded and core-targeting drug nanoparticles were loaded into the mesoporous silica nanoparticle carriers by vacuum adsorption to form a core layer.

[0058] Temperature-sensitive polymers were synthesized on the surface of mesoporous silica nanoparticle carriers via RAFT polymerization, and functional components were embedded into the temperature-sensitive polymers to form an intermediate layer.

[0059] The intermediate layer particles were dispersed in an aqueous solution of methacryloyl gelatin, and after the addition of photoinitiators and additives, they were cured using ultraviolet light to form an outer shell layer, thus obtaining a bio-nanomaterial for the treatment of retroperitoneal liposarcoma.

[0060] Experimental Example

[0061] To verify the performance of the bio-nanomaterials prepared by this method, a nude mouse orthotopic liposarcoma model of human dedifferentiated liposarcoma was established. Experiments were then conducted with a saline group, a trabectedine monotherapy group, and a group using the bio-nanomaterials prepared by this method, respectively, to verify the effects of the three components on the orthotopic liposarcoma in nude mice. The experimental results are shown in the table below:

[0062] Group Tumor volume reduction rate Recurrence rate (8 weeks) CD8+ T cell infiltration rate saline group - 100％ 5.2±1.1％ Anlotinib monotherapy group 45.7％ 53％ 14.5±1.8％ Bionanomaterials Group 82.4％ 16.7％ 32.6±3.4％

[0063] As shown in the table above, the tumor volume of nude mice injected with saline did not shrink, and the recurrence rate at 8 weeks did not decrease. The CD8+ T cell infiltration rate was 5.2±1.1%, which was relatively low. In the anlotinib monotherapy group, the tumor volume of nude mice shrank by 45.7%, the recurrence rate at 8 weeks decreased to 53%, and the CD8+ T cell infiltration rate increased to 14.5±1.8%. The tumor volume reduction rate of nude mice injected with the bio-nanomaterial prepared by this method reached 82.4%, which was significantly higher than the corresponding values ​​in the saline group and the anlotinib monotherapy group, indicating that the bio-nanomaterial has a significant inhibitory effect on tumors. The recurrence rate at 8 weeks decreased to 16.7%, which was significantly lower than the corresponding values ​​in the saline group and the anlotinib monotherapy group, indicating that the bio-nanomaterial can effectively inhibit tumor recurrence. At the same time, the CD8+ T cell infiltration rate of nude mice in this group reached 32.6±3.4%, which was significantly higher than the other two groups, indicating that the immune system activity of nude mice treated with bio-nanomaterial was significantly enhanced.

[0064] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0065] The accompanying drawings of the embodiments disclosed in this invention only involve structures relevant to the embodiments disclosed in this invention. Other structures can be referred to with common designs. Unless otherwise specified, the same embodiment and different embodiments of this invention can be combined with each other.

Claims

1. A bio-nanomaterial for the treatment of retroperitoneal liposarcoma, characterized in that, It includes a core layer, an intermediate layer and an outer shell layer. The core layer is composed of mesoporous silica nanoparticle carriers and loaded drugs. The intermediate layer is composed of temperature-sensitive polymers and functional components. The outer shell layer is composed of a hydrogel shell and additives.

2. The bio-nanomaterial for treating retroperitoneal liposarcoma according to claim 1, characterized in that: The loaded drugs include anlotinib, pebocilib, MDM2 inhibitors, trabectedin, and siRNA.

3. The bio-nanomaterial for treating retroperitoneal liposarcoma according to claim 1, characterized in that: The surface of the mesoporous silica nanoparticle carrier is modified with folic acid and hyaluronic acid.

4. The bio-nanomaterial for treating retroperitoneal liposarcoma according to claim 1, characterized in that: The temperature-sensitive polymer is N-isopropylacrylamide-co-acrylic acid, and the functional components include PD-1 antibody covalent conjugate and interleukin-12 sustained-release microspheres.

5. The bio-nanomaterial for treating retroperitoneal liposarcoma according to claim 1, characterized in that: The hydrogel shell is a methacrylamide gelatin hydrogel, and the additives include platelet-derived growth factor and nano-hydroxyapatite.

6. The bio-nanomaterial for treating retroperitoneal liposarcoma according to claim 5, characterized in that: The additives also include polycaprolactone-polyethylene glycol-polycaprolactone, hyaluronic acid-polylysine grafts, and polyethylene glycol-polydopamine.

7. The bio-nanomaterial for treating retroperitoneal liposarcoma according to claim 4, characterized in that: The functional components also include a PI 3K / mTOR dual-target inhibitor, liposome-encapsulated doxorubicin, and a β3-adrenergic receptor antagonist.

8. The bio-nanomaterial for treating retroperitoneal liposarcoma according to claim 4, characterized in that: The functional components also include matrix metalloproteinase-2 responsive peptides.

9. The bio-nanomaterial for treating retroperitoneal liposarcoma according to claim 1, characterized in that: The steps for preparing bio-nanomaterials include: Mesoporous silica nanoparticle carriers were synthesized using the sol-gel method, and drugs were loaded into the mesoporous silica nanoparticle carriers by vacuum adsorption to form a core layer. Temperature-sensitive polymers were synthesized on the surface of mesoporous silica nanoparticle carriers via RAFT polymerization, and functional components were embedded into the temperature-sensitive polymers to form an intermediate layer. The intermediate layer particles were dispersed in an aqueous solution of methacryloyl gelatin, and after the addition of photoinitiators and additives, they were cured using ultraviolet light to form an outer shell layer, thus obtaining a bio-nanomaterial for the treatment of retroperitoneal liposarcoma.

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