Fabrication And Property Study Of Environment-Responsive Shell Cross-Linked Micelles

In the past decade, nanoparticles and its application in drug delivery system have attractedgreat attention and became a hot topic, because they have passive targeting ability in tumor tissuewhich has the enhanced permeation and retention effect (EPR effect). Due to the long bloodcirculation, improved water solubility, and facile integration of functionalities, the tumormicroenvironments-responsive polymeric micelles as novel anticancer drug vectors show the greatpotential application. The disulfide bond is reduction-sensitive and is prone to rapid cleavage at atime scale from minutes to hours under a reductive environment. And the structure of ortho estershave the acid-sensitive property, it will be degradable under weakly acidic conditions. Since thereduction in tumor cells is much higher than in body circulation and extracellular milieus, and thepH in tumor cells is much lower, so the micelle based on polymer which contain the disulfidebond and the structure of ortho esters have the great potential to be used as the drug carriers toachieve the controlled-release of the drug.The major works of this paper are: A well-defined poly[(ethylene glycol)-block-2-(dimethylamino)ethyl methacrylate-block-2-(diethylamino) methacrylate](PEG-b-DMA-b-DEA) triblock copolymer was synthesized via atom transfer radical polymerization (ATRP) bysuccessively polymerization of DMA and DEA monomers using a PEG-based macroinitiator, andobtained copolymer was then converted to be PEG-b-P(DMA-co-QDMA)-b-PDEA copolymerwith “clickable” moieties in the middle block by the quaternization with propargyl bromide. Thenthe cross-linkers1,6-bisazidehexane, bis-(azidoethyl)disulfde which contains thereduction-sensitive disulfide bond and4-Azidomethyl-2-Azidohexyloxy-[1,3]-dioxolan whichcontains the structure of ortho esters were synthesized. Herein, the novel tumormicroenvironments-responsive SCL micelles with pH-responsive cores from poly[(ethyleneglycol)-block-propargyl bromide partially quaternized2-(dimethylamino)ethylmethacrylate-block-2-(diethylamino)ethyl methacrylate],[PEG-b-(DMA-co-QDMA)-b-DEA] bychoosing1,6-bisazidehexane, bis-(azidoethyl)-disulfde and4-Azidomethyl-2-Azido-hexyloxy-[1,3]-dioxolan as new cross-linkers were prepared via click chemistry, and also the size, size distribution and the degradable behavior of the environments-responsive SCL micelles werestudied in this work.