Poly(thioether phenyl acrylate) Based Micelles Show Exclusively ROS-triggered Breakdown

In certain tumor and diseased tissues, reactive oxygen species (ROS), such as H2O2, are produced in higher concentrations than in healthy cells. To date, only few examples of drug delivery and release systems responds selectively to these small but significantly elevated ROS concentrations. In addition, assuring the stability of the polymer-based carrier in “healthy” biological conditions is still a challenge in the field of oxidation-sensitive materials. Here, we present ROS-responsive block copolymer micelles capable of achieving micellar disruption over days in the presence of 2 mM H2O2 and within hours under higher concentrations of H2O2 (60 – 600 mM). At the same time, these micelles are stable for over two weeks in oxidant-free physiological (pH = 7.4, 37°C) and for at least six days in mildly acidic (pH = 5.0 and pH = 6.0, 37°C) conditions. The observed selectivity is programmed into the material using a 4-(methylthio)phenyl ester based logic gate. Here, oxidation of the thioether moiety results in a large increase in ester hydrolytic lability, effectively switching the ester hydrolysis from off to on. The concept represents a step forward to realize signal responsive drug delivery materials capable of selective action in biological environments.

Self-regulated co-assembly of soft and hard nanoparticles

Controlled self-assembly of colloidal particles into predetermined organization facilitates the bottom-up manufacture of artificial materials with designated hierarchies and synergistically integrated functionalities. However, it remains a major challenge to assemble individual nanoparticles with minimal building instructions in a programmable fashion due to the lack of directional interactions. Here, we develop a general paradigm for controlled co-assembly of soft block copolymer micelles and simple unvarnished hard nanoparticles through variable noncovalent interactions, including hydrogen bonding and coordination interactions. Upon association, the hairy micelle corona binds with the hard nanoparticles with a specific valence depending exactly on their relative size and feeding ratio. This permits the integration of block copolymer micelles with a diverse array of hard nanoparticles with tunable chemistry into multidimensional colloidal molecules and polymers. Secondary co-assembly of the resulting colloidal molecules further leads to the formation of more complex hierarchical colloidal superstructures. Notably, such colloidal assembly is processible on surface either through initiating the alternating co-assembly from a micelle immobilized on a substrate or directly grafting a colloidal oligomer onto the micellar anchor.