Tuning the Structure, Stability, and Responsivity of Polymeric Arsenical Nanoparticles Using Polythiol Cross-Linkers

The use of organic arsenicals in polymer chemistry and biomaterials science is limited despite the distinctive and versatile chemistry of arsenic. The interchangeable oxidation states of arsenic and the subsequent changes in chemical properties make it a promising candidate for redox-responsive materials. Thus, reversible addition–fragmentation chain transfer (RAFT) polymerization has been employed for the first time to synthesize thermoresponsive organic arsenical containing block copolymers. The polymers undergo simultaneous self-assembly and cross-linking, via the organic arsenical pendant groups, under reductive conditions (to reduce As­(V) to As­(III)) in the presence of polythiol reagents as cross-linkers. The formation of As–S bonds stabilizes the nanoparticles formed (D_h = 19–29 nm) and enables the stability and responsivity to oxidative stress of the particles, in aqueous and model biological solutions, to be tuned as a function of the number of thiols in the cross-linker or the [SH]/[As] stoichiometric ratio. The parent block copolymers and nanoparticles are nontoxic in vitro, and the tunable responsivity of these nanoparticles and the (bio)­chemical activity of organic arsenical reagents could be advantageous for targeted drug delivery and the other bio­(nano)­medical applications. To the best our knowledge, this is the first time that arsenic–thiolate (As–S) bonding has been employed for stimuli-responsive cross-linking of polymeric nanoparticles.