Application Of Cationic Nanocarriers With Photodynamic Properties In Cancer Therapy

Cancer is one of the most serious diseases that threaten human life in modern society.Due to the complexity,diversity and heterogeneity of tumors,traditional treatment methods are inefficient to cure cancer completely.The development of effective and safe cancer multimodal therapy is an urgent task to the scientific community currently.Gene therapy(GT)and photodynamic therapy(PDT)are two burgeoning and effective anti-cancer methods.However,the preparation of gene carriers with high transfection,low toxicity and multi-functionality still needs further research.Firstly,we synthesize the nanoparticles PRB obtained from the reaction of photosensitizer(PS)rose bengal and dopamine(DA)in the second chapter of the paper.By controlling the ratios of rose bengal 94 and DA,PRB nanoparticles can be prepared with different contents of rose bengal.After the surface modification with cationic polymer PGED,nanoparticles PRB-PGED(PRP)with various functions were flexibly prepared.By studying the in vitro and in vivo experiments of PRP nanoparticles,it has been proved that PRP nanoparticles have high transfection,low toxicity and strong phototoxicity.And results exhibit excellent anticancer ability of PRP in a 4T1 tumor model of nude mice benefitting from multimodality PDT/GT treatment.In addition,PRP nanoparticles can be excited at a wavelength of 575 nm to monitor the distribution of the vector in vivo as fluorescence probe.In addition,based on the second chapter,we design a gene carrier that can use ROS produced by PDT to realize self-degradation.Cationic polymer PGEA was modified on cyclodextrin(CD)by classical ATRP and four-arm molecules were prepared by using amidation reaction to modify Fc with phthalocyanine.The oxidizable supramolecular gene was prepared by the self-assembly of ?-CD and Fc.Due to the photochemical internalization(PCI)technology,phthalocyanine induces reactive oxygen species(ROS)upon the induction of visible light,allowing carriers to release from the endo/lysosomes without causing direct cell death or nucleic acid inactivation.And the resulting ROS will induce the carrier to disassemble and degrade.Specific in vivo and in vitro experiments were followed to verify the high transfection and low toxicity of the material.The obtained self-assembly supramolecular nanoparticles can disassemble in response to the oxidative environment of the cells,thus providing a new platform for anti-cancer research.In summary,we have prepared a series of gene carriers with high transfection and low toxicity.And good anti-tumor effects by controlling the light conditions were demonstrated,thus providing active guidance for the subsequent clinical anticancer career.