Functional Drug Nanocarriers Prepared Via ATRP And Their Controlled Release Behavior

Almost all the anticancer drugs cause severe side effects on normal tissues and organs due to their nonspecific delivery. Thus tumor-targeting delivery of anticancer drugs remains a serious challenge in clinical cancer treatment. Functional polymeric drug carriers have attracted extensive attention and considerable research interests due to their unique chemical structure, excellent physicochemical properties and great potential applications. Because variety of materials, such as monomer, initiator, etc, it is possible to synthesize kinds of functional polymeric drug carriers, such as biocompatibility, pH responsiveness, reducing responsiveness, temperature sensitivity, targeting, which could deal with different treatment. Therefore, different functional polymeric drug carriers were prepared, and then research the drug release behavior.A facile strategy was established for the pH/reductant dual-responsive corecrosslinked(CCL) micelles via in-situ atom transfer radical polymerization(ATRP), the micelles also held biocompatibility and targeting, then relying on TEM, DLS, FTTR or other characterization techniques to obtain its morphology and structure. The micelles were hydrolyzed to obtain PAA blocks which could load DOX via electrostatic interaction. And, multiple responsiveness was studyed by the in vitro drug release behavior of the DOX-loaded micelles which evaluated in different stimulated media(different pH or reducing agent), and the result demonstrating the excellent tumor microenvironment responsive controlled release behavior upon acidic media with high level GSH.For better drug-loading possibility and capability, a new type of multi-functional polymeric hollow nanocapsules(PHN) were synthesized in a miniemulsion interfacial polymerization via activator generated electron transfer atom transfer radical polymerization(AGET ATRP) technique, and relying on TEM, DLS, FT-TR or other characterization techniques to obtain its morphology and structure. The nanocapsules owned unique hollow structure, which led to extremely high drug-loading capability. It also showed that the existence of folate group significantly improved pH stimuliresponsive and DOX-loading capacity of the polymeric nanocapsules. As a drug carrier for DOX, the tumor micro-environment characteristics, such as the presence of GSH and acidic media, would accelerate the DOX release. After loading of DOX, the DOXloaded HPHN expressed the similar cell killing ability as the free DOX, although the HPHN was non-toxic.The novel biocompatible reduction and pH dual-responsive CCL micelles were synthesized via atom transfer radical polymerization(ATRP) with the hyperbranched polymer which obtained by SCVCP as multi-functional macroinitiator, and relying on TEM, DLS, FT-TR or other characterization techniques to obtain its morphology and structure. Under different environments(normal or cancer cells), the drug-loaded micelles were triggered by kinds of environment factors, thus, different release behaviors were obtained to explore and analyze dual- responsive of micelles. The in vitro release showed that higher GSH concentration and/or lower pH value would lead to a faster and more efficient DOX release. Besides, biological feasibility of the micelles was proved by cytotoxicity.