| As the major public health problem of the world,cancer is currently threatening human health.Clinical methods for cancer treatment include surgery,chemotherapy and radiotherapy.Although these traditional methods can achieve a certain therapeutic effect,problems such as drug resistance,toxicity to normal tissues,and metastases of the lesions still remain,resulting in inefficiency of treatment.With the continuous research and exploration of cancer treatment,many new therapeutic methods such as photodynamic therapy,photothermal therapy and immunotherapy have emerged in recent years.Although these new treatments can overcome some of the shortcomings of traditional treatments,they still have their own problems in practical use.For example,the treatment resistance caused by hypoxia in the tumor tissue during photodynamic therapy will lead to therapeutic resistance and low therapeutic efficiency.And heat shock proteins in cancer cells lead to the resistance of tumor cells to photothermal treatment-induced apoptosis.How to develop new therapeutic strategies to ameliorate the problems of new therapeutic methods and improve the efficiency of cancer treatment is a hot research topic at present.Covalent organic frameworks(COF),one of the most important porous materials following mental organic frameworks(MOF)is a rapidly developing field in chemical research.COF is widely used in a variety of fields,such as photoconductive devices,heterogeneous catalysis and energy storage,separation and adsorption.In addition,COF is gradually exerting their unique advantages in the field of biomedical science.The porosity of COF can be used to encapsulate drug molecules with a high encapsulation rate.Some of the COF can be used as photosensitizers for photodynamic therapy due to their special optical properties.Additionally,using the unique modular structure of COF,it is easy to modify various molecules on the surface and realize a variety of biological applications.In this paper,two kinds of COF nanocomposites were designed and synthesized based on the covalent organic framework of porphyrins,selenium nanoparticles,and gambogic acid for the improved treatment of anti-tumor by photodynamic/photothermal therapy.Specifically,it includes the following two aspects of work:1.A new type of COF modified with Se NPs was synthesized as nanomedicine to realize the photodynamic and selenium synergistic enhanced cancer therapy.Se NPs were modified by in situ reduction on the surface of porphyrin COF nanoparticles,and finally,polyethylene glycol(PEG)was further bonded on the surface of Se NPs-modified COF nanoparticles through the aldehyde amine condensation reaction(Se@COF-PEG).On the one hand,COF can prevent the agglomeration of adjacent selenium nanoparticles,which makes them have high stability.On the other hand,porphyrin ligands can produce reactive oxygen species under laser irradiation,which can effectively kill cancer cells and effectively inhibit tumor growth in the early stage of treatment.Meanwhile,Se NPs can induce mitochondrial dysfunction to produce ROS to kill cancer cells during the entire treatment period,enabling Se NPs-mediated cancer therapy(Se T)to provide long-term inhibition of tumor growth throughout the treatment cycle.The surface modified polyethylene glycol(PEG)greatly improves the biocompatibility and biostability of nanodrugs.The combination of photodynamic therapy and selenium nanoparticles can overcome the problem of reduced therapeutic efficiency of PDT due to the tumor hypoxia,effectively inhibiting tumor growth and recurrence.This work provides a new insight to solve the resistance problem caused by tumor hypoxia during PDT treatment.2.A kind of nano-COF doped with gambogic acid was designed and synthesized for low temperature photothermal therapy of tumor.The selected porphyrin-based COF can achieve photothermal therapy under the irradiation of a single laser wavelength,increasing the temperature of the tumor tissue increases under the irradiation of 635 nm laser,which plays a killing role on tumor cells.As an inhibitor of heat shock protein 90,gambogic acid can specifically target and lower the heat shock protein in the cytoplasm,thereby restoring the thermal sensitivity of cells to temperature,In this way,cancer cells can undergo apoptosis at low temperature(about 45 ?),and realize efficient low temperature photothermal therapy.This work provides a new idea for solving the problem of resistance of tumor cells to photothermal therapy caused by heat shock proteins during photothermal therapy. |
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