Nicky Chan

Dual location disulfide degradable interlayer-crosslinked micelles with extended sheddable coronas exhibiting enhanced colloidal stability and rapid release

Amphiphilic block copolymer-based micellar nanocarriers hold great promise as a drug delivery platform; however, the colloidal stability of nanoassemblies upon intravenous injection remains a significant challenge. Further, enhanced/controlled release of encapsulated drugs by cleavage of dynamic covalent linkages in response to external stimuli is highly desired. Herein, we report new polylactide (PLA)-based triblock copolymers (PssDL) possessing thiol-responsive dynamic disulfide linkages at dual locations using a combination of ring opening polymerization and controlled radical polymerization techniques. These well-defined PssDL copolymers are designed to self-assemble to form aqueous micellar aggregates having multiple pendant disulfide linkages in a hydrophobic interlayer as well as single disulfides at interfaces of the interlayer and PLA core, surrounded by hydrophilic coronas. Through thiol-responsive cleavage of these dually located disulfide linkages, novel interlayer-crosslinked micelles (ICMs) with a crosslinkable and sheddable extended corona can be formed, thus combining the enhanced colloidal stability of crosslinked nanocarriers with rapid destabilization or disintegration of micelles typically found with sheddable systems. This dual location degradation process results in enhanced colloidal stability, along with controlled release of encapsulated anticancer drugs to promote the inhibition of cell proliferation after internalization into cancer cells.

Dual Redox and Thermoresponsive Double Hydrophilic Block Copolymers with Tunable Thermoresponsive Properties and Self-Assembly Behavior

The synthesis, tunable thermoresponsive properties, and self-assembly of dual redox and thermoresponsive double hydrophilic block copolymers having pendant disulfide linkages (DHBCss) are reported. Well-defined DHBCss composed of a hydrophilic poly(ethylene oxide) block and a dual thermo- and reduction-responsive random copolymer block containing pendant disulfide linkages are synthesized by atom transfer radical polymerization. Their lower critical solution temperature (LCST) transitions are adjusted through modulating pendant hydrophobic-hydrophilic balance with disulfide-thiol-sulfide chemistry. Further, these DHBCss derivatives are converted to disulfide-crosslinked nanogels at temperatures above LCST through temperature-driven self-assembly and in situ disulfide crosslinking. They exhibit enhanced colloidal stability and further reduction-responsive degradability, thus demonstrating versatility of dual thermo- and reduction-responsive smart materials.

Thiol-responsive hydrogel scaffolds for rapid change in thermoresponsiveness

A facile strategy to fabricate thiol-responsive thermoresponsive hydrogels able to rapidly change their volume in response to temperature is reported. The strategy utilizes crosslinking atom transfer radical polymerization to synthesize well-defined hydrogels of thermoresponsive oligo(ethylene oxide)-based polymethacrylates with a uniform network crosslinked with dynamic disulfides. Thiol-responsive cleavage of disulfide linkages to the corresponding pendant thiols allows for the generation of hydrophilic dangling chains in the hydrogels as well as the increase in hydrophilicity of the hydrogel network. The degraded hydrogels exhibit a rapid change of thermoresponsiveness (deswelling kinetics) with a slight sacrifice in mechanical properties. Evaluating the hydrogels from a biomedical perspective, rapid thermoresponsive hydrogels are non-cytotoxic and exhibit enhanced release of encapsulated model drugs.

Designing Hydrogels by ATRP

This review summarizes the recent progress on the synthesis and application of covalently crosslinked hydrogels prepared using atom transfer radical polymerization (ATRP) technique. ATRP has been employed as an effective means to synthesize well-controlled polymeric materials with narrow molecular weight distributions, compositions, chain-end functionalities, and macromolecular architectures. These ATRP-processed materials include not only linear polymer chains but also various branched architectures such as star, gradient, and graft copolymers with a very high grafting density. The techniques can be successfully used in water under homogeneous or heterogeneous conditions opening new avenues for the preparation of hydrogels and other networks, including functional materials, responsive, injectable and supersoft elastomers suitable for multiple bio-related applications.