Targeted Bioresorbable Polymersomes for the Delivery of Cisplatin

Chemotherapy today is often plagued by major side effects due to anticancer drugs damaging healthy tissues in addition to cancer cells. These side effects can often be mitigated by encapsulating chemotherapeutics in a targeted drug delivery system. One of the most promising systems is the polymersome, a self-assembled nanoscale aggregate of amphiphilic polymers that has the potential to emerge as a long-circulating, robust carrier capable of encapsulating both hydrophilic and hydrophobic payloads. 

We have developed a nontoxic, polymersome-forming, bioresorbable polymer that can efficiently and site-selectively tether targeting peptides under mild conditions (water at pH 7.4) without the need for potentially toxic catalysts. Here we characterize delivery and release using these polymersomes to human colon cancer cells overexpressing the α₅β₁ integrin. We demonstrate that delivery efficacy using these carriers can be markedly improved over commonly-used RGD targeting peptides by targeting these receptors with the next-generation targeting peptide PR_b. Further, delivery is demonstrated to be specific to cells overexpressing the integrin with minimal delivery observed in a cell line that does not overexpress the receptor. Finally, we encapsulate the anticancer drug cisplatin and demonstrate that PR_b targeting can greatly improve delivery efficacy to human colon cancer cells with commensurate gains in cisplatin-induced cell death. These results demonstrate that our polymersomes may be an attractive route to minimizing side effects associated with current cisplatin chemotherapy.