Controlled Preparation Of Cationic Polymer/Gold Nanorod Complexes And Their Biomedical Applications

With the changes in the environment,more and more cancer patients appear in China,and because of the late discovery and the lack of efficient treatment,there is a high mortality rate of cancer patients.This phenomenon has a great threat to people's health.Therefore,early diagnosis and treatment of cancer is urgent.Traditional chemotherapy and radiotherapy could not solve the difficulties faced in the current cancer treatment.Gene therapy,which is a highly effective treatment of cancer,is a new way in theory,but in the actual operation the development of gene therapy face the bottlenecks,mainly in how to build a low toxicity and efficient gene delivery vector.The cationic non-viral delivery vector has attracted much attention,in which the organic/inorganic nanocomposite delivery carrier has the characteristics of long circulation and easy transmembrane transport,and the inorganic nanomaterials have excellent photoelectromagnetic properties,so that the carrier delivery system possess molecular imaging and functional therapy.The key problem in the construction of organic/inorganic nanocomposite delivery carriers is to select the appropriate functional inorganic nanoparticles and to use simple construction methods in order to achieve better therapeutic effect.First,we selected gold nanorods with unique physicochemical properties,good biocompatibility and low cytotoxicity,and their synthesis were simple and easy to modify.They were characterized by photoacoustic imaging and photothermal therapy.Secondly,we used ATRP(Atom transfer radical polymerization)and ring-opening reaction obtain cationic polymer BUCT-PGED(ethylenediamine functionalized poly(glycidyl methacrylate)and BUCT-PGEA(ethanolamine functionalized poly(glycidyl methacrylate)).Nest,lipoic acid(LA)or lipoic acid anhydride(LA-LA)was successfully linked with BUCT-PGEA and BUCT-PGED to form the desired conjugates(PEGA-LA and PGED-LA)prior to the functionalization process.Finally,the conjugates could be grafted onto Au NRs through multiple dithiolane rings to achieve welldispersed organic/inorganic nanohybrids.The nanocomposite carrier was evaluated in C6 and HeLa cell lines.The results showed that the nanocomposite vector had higher gene transfection efficiency and lower cytotoxicity(compared with PEI);and in vivo imaging and the treatment experiment showed excellent results.We successfully prepared a diagnostic system with dual imaging(CT and PAI)and dual therapy(GT and PTT)through the "Grafting-onto" method.In addition,we selected mesoporous nanosilica with drug-loaded function and magnetic iron oxide with enhanced MR imaging ability.Using self-assembly method(cyclodextrin and adamantane "Host-guest"supramolecular assembly).The gold nanorods and magnetic iron oxide modified with the cationic polymer,and assembled onto the mesoporous silica.The prepared nanocomposite gene delivery assembly was evaluated in HepG2 and C6 cell lines,and the results showed that it had the desired transfection efficiency and low cytotoxicity(compared with PEI).In addition,the assembly can be disassembled by the photothermal property of gold nanorods and magnetic iron oxide.It is conducive to the degradation and removal of materials,nanocomposites can also possess multi-moal imaging and combined therapy.