PEGylated Poly-HDACi: A Designer Polyprodrug from Optimized Drug Units.

We designed, synthesized, and characterized a tri-block copolymer. Its hydrophobic part, a chain of histone deacetylase inhibitor (HDACi) prodrug, was symmetrically flanked by two identical PEG blocks, whereas the built-in HDACi was a linear molecule, terminated with a thiol at one end, and a hydroxyl group at the other. Such a feature facilitated end-to-end linkage of prodrugs through alternatively aligned disulfides and carbonates. The disulfides served dual roles: redox sensors of smart nanomedicine, and warheads of masked HDACi drugs. This approach, carefully designed to benefit both control-release and efficacy, is conceptually novel for optimizing drug units in nanomedicine. Micelles from this designer polyprodrug released only PEG, CO2 and HDACi, and synergized with DOX against HCT116 cells, demonstrating its widespread potential in combination therapy. Our work highlights, for the first time, the unique advantage of thiol-based drug molecules in nanomedicine design.

Poly(N-isopropylacrylamide)/polydopamine/clay nanocomposite hydrogels with stretchability, conductivity, and dual light- and thermo- responsive bending and adhesive properties.

Conducting hydrogels have attracted attention as a special functional class of smart soft materials and have found applications in various advanced fields. However, acquiring all the characteristics such as conductivity, adequate adhesiveness, self-healing ability, stretchability, biocompatibility, and stimulating deformation responsiveness still remains a challenge. Inspired by the mechanism of bioadhesion in marine mussels, a multifunctional nanocomposite hydrogel with excellent adhesiveness to a broad range of substrates including human skin was developed with the help of synergistic multiple coordination bonds between clay, poly(N-isopropylacrylamide) (PNIPAM), and polydopamine nanoparticles (PDA-NPs). The prepared hydrogel showed controllable near-infrared (NIR) responsive deformation after incorporation of PDA-NPs as highly effective photothermal agents in the thermo-sensitive PNIPAM network. Meanwhile, the fabricated nanocomposite hydrogels showed excellent stretchability and conductivity, which make them attractive material candidates for application in various fields, such as electronic skin, wearable devices, and so on.