Tagging red blood cells (RBC) using nanoparticles can offer great advantages for potential applications in drug delivery. The abundance, biocompatibility, and longevity in circulation (about 45 days in mice and 120 days in humans) made the RBC an excellent candidate as a drug shuttle. Also, the drug-carrying agents attached to RBC can be cleared through the pathways that normally eliminate old and damaged red blood cells, which provides a novel approach for targeting these pathways.Therefore, anchoring the drug-loading nanoparticle to the surface of RBCs via a synthetic polymer linker is a promising strategy to improve the solubility of the loaded drugs, extend the time of their circulation, reduce the unintended side effects of the drug, and enhance their efficacy.<br/>It has been widely studied and developed that controlled radical polymerization (CRP) gives predictable molecular weights, low poly dispersity and precise control of the reaction rate. For reversible addition-fragmentation chain transfer (RAFT) reaction, the reaction kinetics is controlled by the chain transfer agent (CTA). The result of RAFT polymerization is a well-defined polymer with low polydispersity. Besides the traditional RAFT reactions, which can be inhibited by oxygen, and are usually only compatible with acrylates, photo-RAFT would be utilized to generate a more diverse library of hydrophilic linkers, with tolerance of oxygen while maintaining a low polydispersity. In this work, we propose to synthesize a polymer with thiol and alkyne functionalities on the chain end, while the thiol can form conjugate with a drug loading agent with a maleimide and the alkyne can undergo click chemistry with an azide present on the antibody.

Synthesis of heterotelechelic polymers via RAFT polymerization for tagging red blood cells as drug carriers

2019 Spring National Meeting

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