LAUSR

Well-defined hydrophilic telechelic dibromo poly(triethyleneglycol monomethyl ether acrylate)s were prepared by single-electron transfer living radical polymerization employing a hydrophobic difunctional initiator containing acetal and disulfide linkages. Despite the resulting homopolymers contain small hydrophobic contents (< 8.5 wt.-% of the entire structure), they are able to self-assemble in water into nanoscale micelle-like particles via chain-folding. Acetal and disulfide linkages were demonstrated to be "keystone" units for their dual stimuli-responsive behavior under biochemically relevant conditions. Their site-selective middle-chain cleavage under both acid pH and reductive conditions splits the homopolymer into two equally-sized fragments and results in the breakdown of the nanoassemblies. The drug loading/delivery potential of theses nanoparticles was investigated using curcumine combining in vitro drug release, cytotoxicity and cellular uptake studies with human cancer cell lines (HT-29 and HeLa). Importantly, this strategy may be extended to prepare innovative nanoplatforms based on hydrophilic homo- or random copolymers for intelligent drug delivery.