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A tumor-mitochondria dual-targeting polymer and its preparation method and application
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A technology of polymers and mitochondria, applied in the direction of antineoplastic drugs, drug combinations, pharmaceutical formulations, etc., can solve problems such as tissue damage, and achieve good biological treatment prospects
Active Publication Date: 2021-08-24
SOUTH CHINA NORMAL UNIVERSITY
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[0003] Photothermal therapy is a new type of physical therapy, which can effectively ablate tumors and release relevant antigens and dangerous signal molecules to change the tumor immunosuppressive microenvironment, but excessive temperature will cause unnecessary damage to normal tissues
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Embodiment 1
[0041] Example 1: Preparation of dual targeting polymer cRGD-P (DMA-co-CSMA)
[0042] (1) Synthesis of light absorber CSMA
[0043] CS-2 was prepared according to reference (J. Am. Chem. Soc. 2012, 134, 1200-1211). Weigh light absorber CS-2 (114mg, 0.203mmol), hydroxyethyl methacrylate (HEMA, 34mg, 0.261mmol), EDC·HCl (60mg, 0.314mmol), DMAP (33mg, 0.27mmol) and 3mL dry Dichloromethane in an ampoule. Freeze the ampoule bottle in liquid nitrogen, pump air with an oil pump, then seal the ampoule bottle, and stir overnight at room temperature. After the solvent was rotary evaporated, it was separated and purified by silica gel column chromatography, and eluted with dichloromethane:ethanol (V:V)=50:1 to obtain the light absorber monomer (CSMA) as a green solid (102.9g, yield: 62% ).
[0044] The reaction formula is:
[0045] (2) Synthetic polymer P(DMA-co-CSMA)
[0046] Add 147.5 mg of N,N-dimethylacrylamide, 2.67 mg of 4-cyanopentanoic acid dithiobenzoate, 0.49 mg of 2,2'...
Embodiment 2
[0049] Example 2: Preparation of targeted, photosensitive antitumor drug R848@cRGD-P(DMA-co-CSMA)
[0050] Dissolve 2 mg of cRGD-P (DMA-co-CSMA) and 0.8 mg of R848 (purchased from Anaiji) in 1.0 mL of N, N-dimethylformamide, stir magnetically at room temperature for 2 hours, and add deionized water dropwise 9mL (dropping rate is 4.5ml / h) and then continue to stir for 1 hour, then dialyze with deionized water, use a dialysis membrane with a molecular weight of 3.5KDa to remove the organic solvent, replace the deionized water every 1 hour during the 4 hours of dialysis, and dialyze Finally, nanoparticles R848@cRGD-P(DMA-co-CSMA) were obtained.
[0051] The ultraviolet absorption spectrum of the dual targeting polymer cRGD-P (DMA-co-CSMA) prepared in Example 1 and the R848@cRGD-P (DMA-co-CSMA) prepared in Example 2 is as follows figure 1 shown, from figure 1 As can be seen in , the dual targeting polymers cRGD-P(DMA-co-CSMA) and R848@cRGD-P(DMA-co-CSMA) have strong absorbance i...
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Abstract
The invention belongs to the field of biomedical polymers, and discloses a tumor-mitochondrion dual-targeting polymer as well as a preparation method and application thereof. In the present invention, the polymer modified by the light absorber CSMA is used to prepare nanoparticles through a self-assembly method. The light absorber CSMA has the function of targeting mitochondria, and the light absorber CSMA in the particle absorbs energy under the trigger of an external trigger source to produce The heat generated by it can damage the mitochondria of the tumor, resulting in immunogenic cell death. The tumor antigens released by the immunogenic tumor cell death and the damage-related model molecules can be further combined with the immune activation loaded in the nanoparticles. As a "personalized vaccine", it can activate the body's immune system to kill tumors and inhibit tumor growth for a long time, so it has a good prospect for biological therapy.
Description
technical field [0001] The invention belongs to the field of biomedical polymers, in particular to a tumor-mitochondrion dual-targeting polymer and its preparation method and application. Background technique [0002] Tumor is the "number one killer" among human malignant diseases, which has been endangering human health. Traditional tumor treatment methods include surgery, chemotherapy and radiotherapy, and these methods often have problems such as incomplete treatment, easy recurrence and drug resistance. In recent years, the rapid development of immunotherapy methods has attracted people's attention, and the above problems have been initially improved. Many studies have shown that both cellular immunity and humoral immunity in the body can generate immune responses to tumor cells, but there are still deficiencies, such as The special microenvironment of the tumor has a strong inhibitory effect on the immune system. Immunotherapy has a long period of action, and it takes ...
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