Bio-inspired zwitterionic polymeric chelating assembly for treatment of copper-induced cytotoxicity and hemolysis

We developed a hemocompatible, bio-inspired, multivalent, polymeric-chelating assembly based on the poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(serinyl acrylate) (PMPC-b-PserA) zwitterionic diblock copolymer. Functional PMPC-b-PserA was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization to catch and encapsulate free copper ions (Cu²⁺) in a solution. PMPC with an identical polar group to phospholipids exhibits high hydrophilicity and fouling resistance against non-specific adsorption, and inertness to the metal ions. On the other hand, PserA with pendant groups of amino acids possesses a strong capability to react with Cu²⁺ by coordination interaction. Therefore, when PMPC-b-PserA was brought into contact with Cu²⁺, a hydrophobic core with multiple coordination "bridges" between polymers and Cu²⁺ was formed, leading to self-assembly of core-shell polymer-metal nanoparticles. As a result, free Cu²⁺ ions can be removed from the solution to prevent damage to cells and tissues. The synthesis and chemical structure of PMPC-b-PserA were characterized, and the formation of self-assembled polymer-Cu²⁺ nanoparticles and colloidal stability were analyzed. More importantly, the detoxification of PMPC-b-PserA in presence of Cu²⁺ with fibroblast cells was demonstrated by increased cell viability >80%. In addition, the hemolysis, which occurred due to disruption of RBC membranes by free Cu²⁺, was effectively suppressed by adding PMPC-b-PserA. The bio-inspired and biocompatible chelating agent of PMPC-b-PserA provides a new treatment approach to encapsulate and detoxify heavy metals in complex media for chelation therapy.