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US-12622877-B2 - Nanocomposite and preparation method and use thereof

US12622877B2US 12622877 B2US12622877 B2US 12622877B2US-12622877-B2

Abstract

The present disclosure provides a nanocomposite and a preparation method and use thereof. In the present disclosure, the nanocomposite is wrapped with Prussian blue nanoparticles (PB) using a platelet membrane (PM) as a shell; and a surface of the PM is modified with an aptamer of cancer cells and horseradish peroxidase (HRP). An ability of platelets (PLTs) to specifically target cancer cells and inflammatory sites can effectively enhance the accumulation of nanoparticles at tumor sites, and help PB better achieve a desirable photothermal therapy (PTT) under near-infrared light irradiation. In addition, hydrogen peroxide is highly expressed in the tumor microenvironment; the HRP modified on a surface of the nanocomposite can decompose the hydrogen peroxide to generate oxygen bubbles, which drive active transport of the nanocomposite, thereby enhancing the accumulation in cancer cells. Modification with the aptamer of cancer cells on a platelet membrane surface enhances cancer cell targeting.

Inventors

  • Yingshu Guo
  • Wenxin Li

Assignees

  • QILU UNIVERSITY OF TECHNOLOGY (SHANDONG ACADEMY OF SCIENCES)

Dates

Publication Date
20260512
Application Date
20221125
Priority Date
20221026

Claims (20)

  1. 1 . A nanocomposite, wherein the nanocomposite material is comprises Prussian blue nanoparticles wrapped by a platelet membrane, and, wherein a surface of the platelet membrane is modified with an aptamer specific for cancer cells and horseradish peroxidase.
  2. 2 . The nanocomposite according to claim 1 , wherein the cancer cells comprise breast cancer cells.
  3. 3 . The nanocomposite according to claim 2 , wherein the aptamer comprises an AS1411 aptamer.
  4. 4 . A method of preparing the nanocomposite according to claim 1 , comprising: 1) Mixing the platelet membrane (PM) and the Prussian blue (PB) nanoparticles to obtain PB/PM nanoparticles; 2) attaching the PB/PM nanoparticles to a well of a plate with a layer of polylysine at the bottom of the well, and adding the horseradish peroxidase to the well of the plate; subjecting the horseradish peroxidase (HRP) and the PB/PM nanoparticles to a dehydration condensation; and separating a product after the dehydration condensation from the well of the plate to obtain PB/PM/HRP; and 3) mixing the PB/PM/HRP and the aptamer specific for the cancer cells to obtain the nanocomposite.
  5. 5 . The method according to claim 4 , wherein the cancer cells comprise breast cancer cells.
  6. 6 . The method according to claim 5 , wherein the aptamer comprises an AS1411 aptamer.
  7. 7 . The method according to claim 4 , wherein the platelet membrane is prepared from platelets; 80 μL to 120 μL of the platelet membrane is prepared from per 1×10 6 of the platelets; the Prussian blue nanoparticles are dissolved in a phosphate-buffered saline (PBS), with a concentration of 0.5 mg/mL to 0.6 mg/mL; and the platelet membrane and the Prussian blue nanoparticles have a volume ratio of (1.2-1.5):1.
  8. 8 . The method according to claim 5 , wherein the platelet membrane is prepared from platelets; 80 μL to 120 μL of the platelet membrane is prepared from per 1×10 6 of the platelets; the Prussian blue nanoparticles are dissolved in a phosphate-buffered saline (PBS), with a concentration of 0.5 mg/mL to 0.6 mg/mL; and the platelet membrane and the Prussian blue nanoparticles have a volume ratio of (1.2-1.5):1.
  9. 9 . The method according to claim 6 , wherein the platelet membrane is prepared from platelets; 80 μL to 120 μL of the platelet membrane is prepared from per 1×10 6 of the platelets; the Prussian blue nanoparticles are dissolved in a phosphate-buffered saline (PBS), with a concentration of 0.5 mg/mL to 0.6 mg/mL; and the platelet membrane and the Prussian blue nanoparticles have a volume ratio of (1.2-1.5):1.
  10. 10 . The method according to claim 4 , wherein the aptamer is a carboxyl-modified aptamer.
  11. 11 . The method according to claim 5 , wherein the aptamer is a carboxyl-modified aptamer.
  12. 12 . The method according to claim 6 , wherein the aptamer is a carboxyl-modified aptamer.
  13. 13 . The method according to claim 4 , wherein the PB/PM/HRP and the aptamer have a mass ratio of (65-70):1.
  14. 14 . The method according to claim 5 , wherein the PB/PM/HRP and the aptamer have a mass ratio of (65-70):1.
  15. 15 . The method according to claim 6 , wherein the PB/PM/HRP and the aptamer have a mass ratio of (65-70):1.
  16. 16 . The method according to claim 10 , wherein the PB/PM/HRP and the aptamer have a mass ratio of (65-70):1.
  17. 17 . The method according to claim 11 , wherein the PB/PM/HRP and the aptamer have a mass ratio of (65-70):1.
  18. 18 . The method according to claim 12 , wherein the PB/PM/HRP and the aptamer have a mass ratio of (65-70):1.
  19. 19 . The method according to claim 10 , wherein the horseradish peroxidase is labeled with biotin; and the PB/PM nanoparticles and the biotin-labeled horseradish peroxidase have a mass ratio of (55-60):1.
  20. 20 . An antitumor drug, comprising the nanocomposite according to claim 1 .

Description

CROSS REFERENCE TO RELATED APPLICATION The present application is a U.S. National Phase application of PCT International Application Number PCT/CN2022/134412, filed on Nov. 25, 2022, which claims priority to the Chinese Patent Application No. 202211315441.1, filed with the China National Intellectual Property Administration (CNIPA) on Oct. 26, 2022, and entitled “NANOCOMPOSITE AND PREPARATION METHOD AND USE THEREOF”, which is incorporated herein by reference in its entirety. REFERENCE TO SEQUENCE LISTING A computer readable XML file entitled “BGI021_001APC”, that was created on Apr. 24, 2023, with a file size of about 2,013 bytes, contains the sequence listing for this application, has been filed with this application, and is hereby incorporated by reference in its entirety. TECHNICAL FIELD The present disclosure belongs to the technical field of biomedicine, and in particular relates to a nanocomposite and a preparation method and use thereof. BACKGROUND Cancer medically refers to malignant tumors originating from epithelial tissue, and is the most common type of malignant tumors. Cancer is still a big problem in medicine until now. Although scientists continue to explore and make great achievements in this field, there are still many unknown problems to be solved. The ideal outcome of an effective anticancer therapy should include the elimination of primary tumors and the sustained suppression of development of metastatic tumors. Currently, the commonly used treatment methods include surgery, chemotherapy, phototherapy, and immunotherapy. However, the tumor microenvironment is characterized by dense extracellular matrix, elevated interstitial fluid pressure, hypoxia, and avascular zones. This specificity limits the delivery of nanomaterials to tumor cells, leading to extravasation of nanomaterials back into the bloodstream. Due to the particularity of the above-mentioned tumor sites, exploratory studies have determined that monotherapy is difficult to achieve a desirable tumor elimination effect, let alone inhibit primary tumor metastasis. Therefore, in order to improve the therapeutic efficacy against tumor cells, multimodal synergistic therapy is urgently needed. SUMMARY A purpose of the present disclosure is to study a nanocomposite and a preparation method and use thereof. In the present disclosure, the accumulation of Prussian blue nanocomposites in tumor sites can be effectively enhanced and a targeting effect on tumor cells can be enhanced. The present disclosure provides a nanocomposite, where the nanocomposite material is composed of prussian blue nanoparticles wrapped by platelet membrane, and a surface of the platelet membrane is modified with an aptamer of cancer cells and horseradish peroxidase. Preferably, the cancer cells include breast cancer cells. Preferably, an aptamer of the breast cancer cells includes an AS1411 aptamer. The present disclosure further provides a preparation method of the nanocomposite, including the following steps: 1) mixing the platelet membrane and the Prussian blue nanoparticles to obtain PB/PM nanoparticles;2) attaching the PB/PM nanoparticles to a well plate with a layer of polylysine at a bottom, and adding the horseradish peroxidase to the well plate; subjecting the horseradish peroxidase and the PB/PM nanoparticles to dehydration condensation; and separating a product after the dehydration condensation from the well plate to obtain PB/PM/HRP;3) mixing the PB/PM/HRP and the aptamer of cancer cells to obtain the nanocomposite. Preferably, the platelet membrane is prepared from platelets; 80 μL to 120 μL of the platelet membrane is prepared from per 1*106 of the platelets; the Prussian blue nanoparticles are dissolved in a phosphate-buffered saline (PBS), with a concentration of 0.5 mg/mL to 0.6 mg/mL; and the platelet membrane and the Prussian blue nanoparticles have a volume ratio of (1.2-1.5):1. Preferably, the aptamer of cancer cells is a carboxyl-modified aptamer of cancer cells. Preferably, the PB/PM/HRP and the aptamer of cancer cells have a mass ratio of (65-70):1. Preferably, the horseradish peroxidase is labeled with biotin; and the PB/PM nanoparticles and the biotin-labeled horseradish peroxidase have a mass ratio of (55-60):1. The present disclosure further provides use of the nanocomposite or a nanocomposite prepared by the preparation method in preparation of an antitumor drug. The present disclosure provides a nanocomposite, where the nanocomposite uses platelet membrane (PM) as a shell to wrap Prussian blue nanoparticles (PB); and a surface of the platelet membrane is modified with an aptamer of cancer cells and horseradish peroxidase (HRP). In the present disclosure, PB that has a desirable light-to-heat conversion efficiency and PM that protects the nanomaterial from immune clearance are combined. An ability of platelets (PLTs) to specifically target cancer cells and inflammatory sites can effectively enhance the accumulation of nanoparticles a