Drug delivery faces challenges due to low selectivity, limited solubility, and widespread systemic distribution of many therapeutic agents. One strategy for solving these issues is to use polymeric nanomaterials. Our lab has previously demonstrated the utility of graft-through polymerization via ring opening metathesis polymerization of peptide-based monomers in the preparation of enzyme-responsive amphiphilic block copolymers and nanoparticles. Proteolytic susceptibility of these materials is mediated by modification of sequence identity and degree of polymerization.  This makes it possible to couple bioactivity with resistance to enzymatic degradation in the application of peptides in therapeutics. Herein, we describe the graft-through copolymerization of norbornene monomers incorporating both targeting peptides and theranostic moieties. We hypothesize that covalent linkage of therapeutic moieties to peptide-based delivery systems may ultimately eliminate delivery problems associated with non-covalent drug encapsulation and simultaneously increase the efficacy of the therapeutic over free drug. Direct polymerization allows for precise control of drug-to-polymer ratio and spatial orientation in the generation of robust and highly reproducible materials. Drug-peptide copolymers that self-assemble into well-defined nanoparticles can also be achieved by tuning the block lengths and identities, providing additional control over properties. Towards this goal, we have synthesized a small library of copolymer systems incorporating several classes of small-molecule therapeutics with various targeting peptides and studied their transduction into cells in vitro.

Rational design of polymeric nanomaterials incorporating covalently bound therapeutics

248th National Meeting (2014)

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