Length of the Stabilizing Zwitterionic Poly(2-methacryloyloxyethyl phosphorycholine) Block Influences the Activity of...

We report on the synthesis of poly(2-methacryloyloxyethyl phosphorycholine-co-PENAO)-block-poly(methyl methacrylate) core-shell nanoparticles which carry different chain lengths of zwitterionic 2-methacryloyloxyethyl phosphorycholine (MPC) on a nanoparticle surface. The particles, 30-40 nm in size, were readily obtained by polymerization-induced self-assembly (PISA) of the corresponding arsenic-based MPC polymers as the stabilizer block and methyl methacrylate (MMA) as the core-forming block. Zwitterionic nanoparticles are ideal candidates for protein-repellent materials. Herein, we show how the decrease of zwitterionic chain lengths tunes the reactivity and cytotoxicity of the organoarsenical anticancer drug PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid). More cytotoxic (5-fold) nanoparticles were obtained when the MPC chain lengths were condensed from 37 to 13 repeating units. To gain a better understanding of the behavior of the drug-directed PISA particles, small-angle neutron scattering (SANS) experiments were conducted, evidencing that having PENAO located in the hydrophilic building block indeed influences the physiochemical micelle structure in terms of core radius (r_core), SLD, shell thickness, and aggregation number.