Study On Concurrent Chemoradiotherapy Of Tumor Microenvironment Responsive Nanoparticles

In recent years,due to various deficiencies of a single treatment,clinical treatment of cancer often takes two or more treatments combined therapy,of which the most widely used is the concurrent chemoradiotherapy.On the other hand,the versatile physical and chemical properties of emerging nanomaterials and the rapid development of nanobiotechnology provide a promising research direction for tumor chemoradiotherapy.The research content of this paper focuses on the two aspects of cancer concurrent chemoradiotherapy.The first part,we mainly designed a kind of nanoparticles effective in radiotherapy and sensitization under hypoxic conditions for cancer concurrent chemoradiotherapy.By modifying the metronidazole monomer on the prodrug and the nano delievery,on the one hand,the characteristics of small particle size and high load are achieved.On the other hand,metronidazole-modified nanoparticles can simultaneously achieve radiosensitization and deliver hypoxic-responsive drugs to hypoxic tumors due to the effective radiosensitization ability under hypoxic conditions and hypoxic triggering structural transformation.Finally,in-vivo experiments prove that the nanodrug delievery system has excellent concurrent chemoradiotherapy.The second part is to formulate the glutathione scavenging vehicle polymer and Pt(?)prodrug together through nanoprecipitation to generate nanoparticles with extra-high drug loading capacity and efficiency.Subsequent experimental data indicated that,upon tumor cell uptake,NPs rapidly disassembled and released cisplatin in response to intracellular GSH while simultaneously consuming GSH to restore Pt sensitivity in cisplatin-resistant tumor cells.The mechanism study revealed that,except for blocking the detoxification of Pt by antioxidants such as GSH,the mitochondrial damage played crucial role in avoiding the efflux of Pt and preventing the escape from apoptosis.Moreover,detailed in vitro and in vivo studies were also carried out to validate the potential and safety of as-prepared prodrug-nanomedicine in both chemotherapy and CRT.