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CN-122005491-A - Bionic nano platform for cooperative therapy and preparation method and application thereof

CN122005491ACN 122005491 ACN122005491 ACN 122005491ACN-122005491-A

Abstract

The invention relates to a synergistic therapeutic bionic nano-platform, which comprises a core and a shell, wherein the core comprises hollow calcium carbonate and manganese carbonate, the shell comprises a cell membrane and fluorescent dye, and the shell is coated on the surface of the core. The preparation method comprises the following steps of synthesis of amorphous calcium carbonate, preparation of hollow calcium carbonate-manganese carbonate nano-particles, cell membrane coating and loading of fluorescent dye. The bionic nano platform for cooperative therapy can integrate various functions of gas release, photo-thermal heat generation, immune regulation, in-vivo imaging and the like, and is used for cooperative therapy of liver cancer.

Inventors

  • GUO RUI
  • LIU HUILING
  • FENG LONGBAO

Assignees

  • 暨南大学

Dates

Publication Date
20260512
Application Date
20260203

Claims (10)

  1. 1. The bionic nano platform for cooperative therapy is characterized by comprising a core and a shell, wherein the core comprises hollow calcium carbonate and manganese carbonate, the shell comprises a cell membrane and fluorescent dye, and the shell is coated on the surface of the core.
  2. 2. The biomimetic nano-platform of claim 1, wherein the cell membrane comprises a liver cancer cell membrane and the fluorescent dye comprises DiR.
  3. 3. The method for preparing the bionic nano-platform according to any one of claims 1 to 2, comprising the steps of: The synthesis of amorphous calcium carbonate, namely dissolving calcium chloride, sealing, placing in a closed drying container filled with ammonium bicarbonate, reacting, centrifuging, washing, dispersing in an organic solvent, and obtaining amorphous calcium carbonate dispersion; Dissolving sodium phosphate, dripping amorphous calcium carbonate dispersion liquid into sodium phosphate solution, reacting, centrifuging, washing and freeze-drying to obtain the hollow calcium carbonate; Dissolving manganese carbonate to obtain manganese carbonate solution, adding hollow calcium carbonate dispersion liquid into the manganese carbonate solution, incubating, concentrating, centrifuging and washing to obtain hollow calcium carbonate-manganese carbonate nanoparticles; cell membrane coating, namely extracting cell membranes, dispersing hollow calcium carbonate-manganese carbonate nano particles in PBS, mixing with the cell membranes, incubating and extruding to obtain the cell membrane coated nano particles; and (3) loading fluorescent dye, namely adding a fluorescent dye solution into the nanoparticle suspension coated by the cell membrane, stirring in a dark place, centrifuging, washing and resuspension to obtain the bionic nano platform.
  4. 4. A method of preparation according to claim 3, characterized in that the synthesis of amorphous calcium carbonate comprises the steps of: Dissolving calcium chloride in a mixed solvent of ethanol and water to obtain a calcium chloride solution, sealing the calcium chloride solution, placing the calcium chloride solution in a closed drying container filled with ammonium bicarbonate, reacting, centrifugally collecting a product, washing, and dispersing in ethanol to obtain an amorphous calcium carbonate dispersion; according to the mass ratio, the calcium chloride and the ammonium bicarbonate are 1 (30-60).
  5. 5. A method of preparation according to claim 3, wherein the preparation of hollow calcium carbonate comprises the steps of: Dissolving sodium phosphate in water, dripping amorphous calcium carbonate dispersion liquid into sodium phosphate solution, stirring for reaction, centrifugally collecting a product, washing and freeze-drying to obtain hollow calcium carbonate; according to the mass ratio, the amorphous calcium carbonate and the sodium phosphate are 1 (6-10).
  6. 6. A method of preparation according to claim 3, characterized in that the preparation of the hollow calcium carbonate-manganese carbonate nanoparticles comprises the steps of: dissolving manganese carbonate in methanol, adding manganese carbonate methanol solution into methanol dispersion liquid of hollow calcium carbonate, incubating, vacuum drying, concentrating, centrifuging, and washing to obtain hollow calcium carbonate-manganese carbonate nano particles; according to the mass ratio, the manganese carbonate is (1-5) and the hollow calcium carbonate is 1.
  7. 7. The method of claim 3, wherein in the cell membrane coating, the cell membrane extraction comprises the steps of: Collecting cells, washing, adding a lysis buffer solution, standing, homogenizing, performing ice bath ultrasound, centrifuging to remove cell nuclei, centrifuging to collect membrane sediment, and re-suspending to obtain a cell membrane suspension; according to the mass ratio, the hollow calcium carbonate-manganese carbonate nano particles are 1-2 in percentage by mass, and the cell membrane is 1-2 in percentage by mass.
  8. 8. A method of preparation according to claim 3, wherein the loading of the fluorescent dye comprises the steps of: Adding a methanol solution of fluorescent dye into the nanoparticle suspension coated by the cell membrane, stirring in a dark place, centrifuging, washing, and re-suspending in PBS to obtain a bionic nano platform; according to the mass ratio, the fluorescent dye is (80-120): 1.
  9. 9. The bionic nano-platform according to claims 1-2 or the bionic nano-platform obtained by the preparation method according to claims 3-8, and the application thereof in preparing medicines for treating liver cancer.
  10. 10. A medicament for treating liver cancer, which is characterized by comprising the bionic nano-platform according to claims 1-2 or the nano-platform obtained by the preparation method according to claims 3-8.

Description

Bionic nano platform for cooperative therapy and preparation method and application thereof Technical Field The invention relates to the field of biological medicine, in particular to a bionic nano platform for cooperative treatment, and a preparation method and application thereof. Background Liver cancer is one of the common and fatal malignant tumors worldwide, and the morbidity and mortality of the liver cancer are in an increasing trend year by year. Currently, the treatment methods of liver cancer mainly comprise surgical excision, chemotherapy, radiotherapy, interventional therapy and the like. However, these conventional treatments have a number of limitations. For example, surgical excision is only suitable for early liver cancer patients, and for middle and late liver cancer patients, due to metastasis and diffusion of tumors, the surgical excision is difficult to completely remove tumor tissues, chemotherapy and radiotherapy can kill tumor cells and cause serious damage to normal tissues and cells, so that a series of serious side effects such as nausea, vomiting, alopecia, immunity decline and the like are caused, and the interventional therapy can be used for locally treating tumors, but has limited treatment effects for some deep or multiple tumors. In recent years, with the development of nanotechnology, nano-drug delivery systems have demonstrated great potential for application in the field of tumor therapy. Some nanoplatforms are designed to carry chemotherapeutic drugs, photothermal agents, etc. to enhance targeting and therapeutic effects of the drug. For example, there are studies to construct nano-systems based on nanoliposomes, polymer nanoparticles, etc. loaded with chemotherapeutic drugs, delivering the drugs to tumor tissue by passive targeting or active targeting. In addition, the photothermal therapy is an emerging tumor treatment method, and the photothermal therapy kills tumor cells by utilizing the thermal effect generated by the photothermal agent under the irradiation of near infrared light, and has the advantages of no wound, high efficiency and the like. However, it is often difficult to achieve the desired therapeutic effect with a single therapeutic modality, as tumor development is a complex process involving multiple signaling pathways and biological processes. Therefore, the multi-mode cooperative therapy strategy becomes a hot spot of current liver cancer therapy research. The existing nanometer treatment platform and the existing multimode treatment strategies still have some defects. On one hand, many nano-platforms lack good tumor targeting and immune escape capability, so that the enrichment efficiency of the medicine in tumor tissues is low, and the medicine is easily recognized and cleared by an immune system, so that the treatment effect is affected. On the other hand, the existing multi-mode treatment strategies often simply combine different treatment modes together, lack effective synergistic effect among treatment mechanisms, and are difficult to realize accurate coupling in space and time, so that the advantages of multi-mode treatment cannot be fully exerted. In addition, some treatments may cause serious side effects during the course of treatment, which have a major impact on the patient's physical health. Disclosure of Invention Aiming at the defects of the prior art, the invention provides a synergistic therapeutic bionic nano platform which comprises a core and a shell, wherein the core comprises hollow calcium carbonate (hCaCO 3) and manganese carbonate (Mn 2(CO)10, which are abbreviated as MnCO hereinafter), the shell comprises a cell membrane and a fluorescent dye, and the shell is coated on the surface of the core. In one embodiment, the cell membrane comprises a liver cancer cell membrane (HCCM) and the fluorescent dye comprises a DiR. The second aspect of the present invention also provides a method for preparing the biomimetic nano platform for cooperative therapy, comprising the following steps: Dissolving calcium chloride (CaCl 2), sealing, placing in a closed drying container filled with ammonium bicarbonate (NH 4HCO3), reacting, centrifuging, washing, and dispersing in an organic solvent to obtain amorphous calcium carbonate dispersion; Dissolving trisodium phosphate (Na 3PO4), dripping amorphous calcium carbonate dispersion liquid into sodium phosphate solution, reacting, centrifuging, washing and freeze-drying to obtain the hollow calcium carbonate (hCaCO 3); Preparing hollow calcium carbonate-manganese carbonate nano particles (hCaCO 3 -MnCO), namely dissolving manganese carbonate to obtain a manganese carbonate solution, adding hollow calcium carbonate dispersion liquid into the manganese carbonate solution, incubating, concentrating, centrifuging and washing to obtain the hollow calcium carbonate-manganese carbonate nano particles; Cell membrane coating, namely, cell membrane extraction, namely, dispersing hollow calcium carbonate-ma