Polymersomes functionalized via “click” chemistry with the fibronectin mimetic peptides PR_b and GRGDSP for targeted delivery to cells with different levels of α5β1 expression

Abstract

Polymersomes were functionalized using azide-alkyne “click” chemistry with two targeting peptides: GRGDSP and the recently designed fibronectin mimetic peptide, PR_b, which has been shown to bind with high specificity to the α₅β₁ integrin expressed on colon cancer cells. The ability of these peptide functionalized polymersomes to achieve targeted delivery to colon cancer cells was assessed by studying their delivery to CT26.WT and Caco-2 cells in vitro. The diblock copolymer poly(ethylene oxide)-b-poly(1,2-butadiene) was synthesized and self-assembled to form polymersomes, which were subsequently functionalized with peptides using a “click” conjugation reaction. Drug delivery efficacy of these peptide functionalized polymersomes loaded with fluorescent markers or the chemotherapeutic, doxorubicin, was assessed and compared. In addition, the cell binding and internalization of fluorescently labeled polymersomes was imaged using confocal microscopy. PR_b functionalized polymersomes are found to significantly outperform both GRGDSP and non-functionalized polymersomes, both in terms of promoting cell binding and internalization and doxorubicin cytotoxicity. Moreover, PR_b functionalized polymersomes are found to act as highly target specific drug delivery agents, thus highlighting them as a promising model targeted drug delivery system.