Length of the Stabilizing Zwitterionic Poly(2-methacryloyloxyethyl phosphorycholine) Block Influences the Activity of the Conjugated Arsenic Drug in Drug-Directed Polymerization-Induced Self-Assembly Particles
2018; American Chemical Society; Volume: 8; Issue: 1 Linguagem: Inglês
10.1021/acsmacrolett.8b00853
ISSN2161-1653
AutoresJanina‐Miriam Noy, Cheng Cao, Martina H. Stenzel,
Tópico(s)Nanoparticle-Based Drug Delivery
ResumoWe 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 (rcore), SLD, shell thickness, and aggregation number.
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