| Compared with traditional treatment methods,polymer nano drugs have very significant advantages compared with traditional treatment methods:they can effectively increase the stability and solubility of tumor treatment drugs,avoid the destruction of drug activity and enable the implementation of drugs Slow and controlled release,increase the amount of drug enrichment in the tumor lesion area,reduce the toxic side effects of the drug on normal tissues,and at the same time realize the targeted treatment of the drug in the lesion area.The environmentally responsive nano drug carrier can effectively realize the release of the drug,and achieve an effective response change by changing the environmental conditions,thereby enabling rapid release of the drug,and finally achieving an increase in the therapeutic effect of the drug.Cells are usually able to maintain their steady state of redox.However,due to the lack of a ROS-eliminating system in the tumor,if the level of ROS is too high and exceeds a certain threshold,selective killing of cancer cells will occur.In addition,radiosensitizers are often used to enhance the radiosensitivity of tumor tissue.However,due to long-term toxicity and poor sensitization effect in the hypoxic environment of tumors,high Z element nanoparticles,small molecule chemicals and various antitumor drugs with sensitization cannot be obtained during radiosensitization.widely used.The development of high-efficiency radiosensitizers has been one of the most important ways to increase the rate of efficacy.In view of this,this paper designed a series of nano drug carriers(PA-Micelle,DOX@HMs and iRGD-DOX@HMs)around the redox response strategy of polymer nanocarrier drugs.Part ?:Through the polymer nanoparticles to enhance the oxidative pressure of tumor cells and inhibit the anti-oxidative ability of cells to cooperate with the treatment of cancer.Cancer cells are more sensitive to elevated tumor oxidative stress than normal cells because they lack a reactive oxygen species elimination system.Oxidative therapy for cancer is to kill cancer cells by selectively increasing oxidative stress in tumor tissues.In this chapter,in order to effectively expand the oxidative therapy,the research team developed polymer nanoparticles which can improve the oxidative stress of tumor and inhibit the antioxidant ability of cancer cells.Amphiphilic block copolymer micelles of poly(ethylene glycol)-b-poly(2-(((4-(4,4,5,5-tetramethyl-1,3,2-dioxaboron heterocyclic pentane-2-yl)benzyl)oxo)carbonyl)ethyl methacrylate](PEG-b-PBEMA)combine with palmitoyl ascorbic acid(PA)to form hybrid micelles(PA-Micelle).Pharmacological concentration of PA molecule as a promoter oxidant,used to up-regulate the level of hydrogen peroxide(H2O2)in tumor site,PBEMA part,showed that H2O2 triggered the release of quinone methylate,used to consume glutathione(GSH),inhibit the antioxidant capacity of cancer cells,cooperate to kill cancer cells,inhibit tumor growth.Given the remarkably low side effects on normal tissues,this new integrated nanoparticle design represents a new class of nanomedical systems for highly efficient oxidation therapy.The nanoparticles exhibit obvious characteristics.Proper size and physical and chemical properties of PA-Micelle micelles ensure the effective enrichment of tumor tissue.Selective cytotoxicity to tumor cells and low impact on normal cells make the system in vivo without obvious damage to normal organs,has high biological safety,and can effectively inhibit the growth of 4T1 tumor.Overall,this new anti-tumor nanoparticle system has shown great potential in clinical applications of certain tumor types,such as breast tumors.Part ?:hypoxia responsive block copolymers are used as radiotherapy sensitizers for radiotherapy of tumors.At present,the performance of small molecular radiosensitizers in vivo is usually affected by the low bioavailability of hypoxic tumor areas.In this chapter,we introduce metronidazole(MN)into biodegradable polypeptide poly(ethylene glycol)-block poly(L-glutamic acid)(PEG-b-PLG)to prepare amphiphilic block copolymer radiosensitizer(PEG-b-P(LG-g-MN),characterize its corresponding properties,and study its cytology and tumor inhibition effect.PEG-b-P(LG-g-MN)grafted with MN can be self-assembled into core-shell micelles in aqueous solution by condensation reaction.Radiosensitizers have been shown to have a higher SER value(2.18)than clinically used sodium glycidazole(GS,SER)of 1.32,and to be exposed to electron beam irradiation.At the time of firing,there is a higher ability of tumor ablation in vivo.Part ?:Hypoxia-responsive block copolymer radiosensitizers as nano-carriers of anticancer drugs to enhance the radiotherapy and chemotherapy of large solid tumors.In this chapter,(PEG-b-P(LG-g-MN)micelle particles can be used to effectively encapsulate doxorubicin(DOX@HMs),a small molecule antitumor drug,by using the amphiphilic block copolymer radiosensitizer(PEG-b-P(LG-g-MN)prepared in Chapter 3 above,after optimizing the ratio of carboxyl to MN groups.MN can transform the hypoxic reactivity structure of anoximidazole,thus triggering the rapid release of DOX@HMs from DOX.After intravenous injection of DOX@HMs into the tail vein of mice,the ablation ability of large solid tumors(?500 mm3)in mice was achieved at low radiation dose(4Gy).Therefore,the novel amphiphilic block copolymer radiosensitizers can be used as both high-efficiency radiosensitizers and hypoxia-responsive DOX nanocarriers for enhanced radiotherapy and chemotherapy.Part ?:To summarize the full text and extend and prospect the next step,in the extension of the previous chapter(Chapter 4),we prepared the iRGD-targeted hypoxic responsive block copolymer radiosensitizer and performed the structure.The characterization is aimed at further enhancing the radiotherapy and chemotherapeutic effect of the hypoxic responsive block copolymer radiosensitizer as an anticancer drug nanocarrier for large-volume solid tumors. |
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