Self-fluorescent Copolymer Anhydride Nanoparticles: Preparation And Pragmatic Application In Drug Delivery And Cell Imaging

Design of high-performance nanocarriers is one of the hottest topics in tumor targeting drug delivery systems. Recently, more and more concerns have been paid to this field, mainly concentrating on multi-drug resistance (MDR effect) and PEG dilemma, both of which has severely affected the anticancer drug (delivered by vehicles) efficiency in the chemotherapy of tumors. Small molecular fluorescent probe has been widely applied as a cell-imaging agent to investigate the endocytosis mechanisms and interactions between the drug carriers and tumor cells (membranes). In this thesis, based on our previous research on fluorescent copolymer anhydrides synthesis, fluorescent copolymer anhydrides (P (dCPS:SA)) were selected as the basic polymer matrix, we continued to further explore and investigate the pragmatic applications of self-fluorescent copolymer anhydride nanoparticles in anticancer drug delivery and cell imaging.According to our previous research, biodegradable copolymer anhydrides, P (dCPS:SA), of a certain molar ratio of dCPS to SA, were readily synthesized via melting co-condensation. FTIR,1H-NMR, GPC and fluorescence spectrophotometer were adopted to characterize the composition, structure and fluorescence property. Results demonstrated P (dCPS:SA)(dCPS/SA=15:85) had been successfully synthesized. Moreover, P (dCPS:SA) has exhibited a strong fluorescent effect.Then, factors which influence the formation and morphology of nanoparticles were extensively investigated via traditional emulsion methods and fluorescent copolymer anhydride nanoparticles had been successfully prepared. DLS, Zeta and TEM were adopted to characterize particle size, surface charge and morphology of the nanoparticles. In addition, confocal laser scanning microscopy (CLSM) was applied to characterize its fluorescent property. Results have confirmed the nanoparticles had a size about120nm and a negative surface charge, meanwhile a strong fluorescent intensity.Finally, anticancer drug (PTX and DOX-HC1) loaded P (dCPS:SA) nanoparticles were prepared via single emulsion method and double emulsion method, respectively. High performance liquid chromatograph and UV/Vis spectrum were adopted to study the drug loading content and drug release profiles. The release behaviors under differently pH values (7.4and5.8) were investigated. Meanwhile, biological evaluation of both drug unloaded and loaded P (dCPS:SA) nanoparticles was carried out by cytotoxicity experiments. The relationship between endocytosis efficiency and incubation time, as well as the distribution of nanoparticles inside cells, were studied via endocytosis experiments in vitro. MTT. flow cytometry and CLSM were adopted to characterize the cytotoxicity, endocytosis efficiency and cell imaging property of fluorescent P (dCPS:SA) nanoparticles. Results have explicitly demonstrated self-fluorescent copolymer anhydrides nanoparticles exhibited obvious pH-dependent release profiles, excellent biocompatibility, a strong fluorescent probe effect and very low endocytosis efficiency. Therefore, self-fluorescent copolymer anhydride nanoparticles have showed a promising prospect in anti-tumor therapy and cell imaging.