(373y) Polymersomes Functionalized with the PR_b Peptide Via Click Chemistry Promote Targeted Drug Delivery to Cancer Cells

Polymersomes, which self assemble in aqueous solutions from amphiphilic block copolymers, have been recognized as a promising system for encapsulation and drug delivery. In this work, peptide-functionalized polymersomes have been synthesized and their performance as a therapeutic tested. Polymersomes were functionalized via azide-alkyne "click" chemistry with two targeting peptides: GRGDSP and the recently designed fibronectin mimetic peptide, PR_b (KSSPHSRN(SG)₅RGDSP). The ability of these peptide functionalized polymersomes to promote targeted delivery to colon cancer cells was assessed by studying their delivery to cancer cells in vitro. The diblock copolymer poly(ethylene oxide)-b-poly(1,2-butadiene) was synthesized and self assembled in aqueous solutions to form polymersomes, which were subsequently functionalized with targeting peptides using a "click" conjugation reaction. The efficacy of targeted delivery to cancer cells was tested for these polymersomes, and PR_b functionalized polymersomes were compared to non-functionalized polymersomes and GRGDSP functionalized polymersomes. Additionally, the chemotherapeutic, doxorubicin, was loaded into these polymersomes and the cytotoxicity of the various targeted polymersome formulations to cancer cells was assayed. PR_b functionalized polymersomes are shown to significantly outperform both non-functionalized polymersomes and GRGDSP functionalized polymersomes as a targeted drug delivery system, both in terms of promoting binding and internalization and doxorubicin delivery and cytotoxicity. Thus, "click" functionalized PR_b targeted polymersomes are identified as an attractive targeted drug delivery vector, capable of delivering a therapeutic load directly into the interior of cancer cells, in an efficient and highly specific manner.