Cancer is currently one of the major causes of death in the world. With the rapid development of nanotechnology, various new nanomaterials have provided new ideas and methods for cancer treatment. Compared with traditional nanomaterials, black phosphorus has potential applications in the biomedical field: drug carriers, new materials for photothermal therapy and photodynamic therapy, and photoacoustic imaging of tumors. In recent years, Chinese scientific researchers have continued to work hard and have successively discovered various ways of using black phosphorus to treat cancer. Some scientific research results have applied for relevant patents, providing theoretical possibilities for the next step of clinical practice.
Method 1: Black phosphorus-based photothermal conversion materials are used to achieve efficient and safe tumor photothermal treatment
Yu Xuefeng, a researcher at the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences, together with Zhang Han, a professor at Shenzhen University, and Zhu Jianhao, a professor at the City University of Hong Kong, used an emulsification solvent evaporation method to prepare a high molecular polymer (PLGA) wrapped black phosphorus quantum dots. (BPQDs) core-shell structured nanospheres (BPQDs/PLGA). As a degradable hydrophobic biomedical polymer, the polymer shell formed by PLGA can isolate the internal black phosphorus quantum dots from the physiological environment, ensuring the stable performance of the black phosphorus quantum dots during the treatment process. After the photothermal treatment, the black phosphorus quantum dots will be slowly released and degraded with the gradual degradation of the PLGA shell, and then safely metabolized out of the body.
Schematic diagram of the in vivo treatment and degradation process of BPQDs/PLGA
Cell and animal experiments have shown that BPQDs/PLGA has good biosafety and passive tumor targeting, and exhibits high photothermal treatment efficiency. Five minutes of near-infrared illumination can effectively treat Kill tumors. The successful development of this new biodegradable photothermal conversion material will undoubtedly promote the actual clinical application of photothermal therapy technology and provide guidance and reference for future biomedical applications of nanomaterials. The research team has applied for relevant invention patents and is actively promoting the application for relevant clinical application licenses, striving to use it in clinical practice as soon as possible.
Method 2: Black phosphorus nanosheets can achieve triple synergistic treatment of photothermal therapy, chemotherapy and biological response to tumors
A research team composed of Tsinghua University Associate Professor Mei Lin, Shenzhen University Professor Zhang Han, Harvard University Professor Shi Jinjun, Dr. Tao Wei and other experts used an optimized liquid exfoliation method to apply black phosphorus two-dimensional nanoflakes to the carrier of diagnostic and therapeutic preparations for the first time Through preparation and functional modification, a “black phosphorus nanosheet carrier system” loaded with the chemotherapy drug doxorubicin was developed. After black phosphorus nanosheets are taken up by tumor cells, they mainly carry out intracellular activities through “macropinocytosis → late endosome → lysosome” and “caveolin-mediated uptake pathway”. The larger two-dimensional black phosphorus nanosheets The specific surface area can lay the foundation for the adsorption of large amounts of chemotherapy drug molecules and improve the drug loading capacity. The loading capacity of black phosphorus nanosheets for doxorubicin is significantly higher than that of traditional polymer nanoparticle carriers, which improves the efficacy of chemotherapy drugs. Black scale nanoflakes can generate local high heat under 808nm laser irradiation. On the one hand, they can be used for photothermal treatment of tumors, and on the other hand, they can also drive the release of drugs.
Research shows that black phosphorus drug-loaded nanosheets have obvious safety and anti-tumor effects in vivo. Experiments have verified that black phosphorus drug-loaded nanosheets have good biocompatibility. The biological response adjustment used in the study Chemotherapy-photothermal therapy combined treatment methods, these multi-modal treatments can accurately treat cancer. At present, this research has made a breakthrough in animal experiments and achieved enhanced tumor suppression effects in immunodeficient nude mice.
Method 3: Effectively combine the chemotherapy of doxorubicin and the photothermal and photodynamic activity of black phosphorus through black phosphorus nanosheets
Professor Liu Younian’s team from Central South University collaborated with Professor Guo Shaojun from Peking University to use the multi-fold structure and negative surface charge of black phosphorus nanosheets to achieve efficient loading of the anti-tumor drug doxorubicin, with a loading capacity as high as 950%. Much higher than the loading capacity of most current nanomedicine carriers. Especially under near-infrared illumination, black phosphorus nanosheets can effectively generate photothermal and reactive oxygen species. On the one hand, photothermal can accelerate the release of doxorubicin and increase the permeability of cell membranes and drug uptake. On the other hand, it can Directly kill tumor cells.
Design and characterization of black phosphorus nanosheets for combined tumor therapy
(a) Black phosphorus nanosheets can efficiently load doxorubicin, enter tumor cells through endocytosis, and trigger rapid release of the drug under light. At the same time, combined with the photothermal and photodynamic activities of black phosphorus, three modes can be combined Kill tumor cells; (b) TEM image of black phosphorus nanosheets; (c-d) Good photothermal properties and photothermal stability of black phosphorus nanosheets; (e-f) UV-visible absorption spectrum and fluorescence spectrum changes prove that doxorubicin Interaction with black phosphorus nanosheets.
In vitro and in vivo experimental results show that through black phosphorus nanosheets, the chemotherapy of doxorubicin and the photothermal and photodynamic activities of black phosphorus can be effectively combined to achieve a combination of three treatment modes and effectively eliminate tumors. In addition, black phosphorus can gradually decompose into phosphate ions that are harmless to organisms in the body. Routine blood analysis and liver and kidney function test results show that�The cells further enter programmed cell death through the pathways of apoptosis and autophagy. For normal cells, due to its weak uptake activity and metabolic rate, the uptake of black phosphorus is small and the degradation is slow, thus maintaining high biocompatibility.
Rohm and Haas resin
Bioactive phosphorus-based drug therapy
In-depth cell and animal experiments have shown that black phosphorus nanosheets exhibit excellent anti-tumor efficacy, and their selective killing effect on cancer cells is far superior to the traditional chemotherapy drug doxorubicin (DOX). The research team calls this selective cancer cell killing effect derived from the natural biological activity of black phosphorus “Bioactive Phosphorus-based Therapy”, or “Active Phosphorus Therapy (BPT)” for short. This study not only demonstrates the great prospects of black phosphorus in the development of nano-chemotherapy drugs, but also reveals new directions for nanomaterials in the field of tumor treatment research. Yu Xuefeng said that further in vivo experimental research is being carried out, but it will take a long time before the drug is actually made.
