Sunflower Polymers for Folate-Mediated Drug Delivery

Polymeric delivery vehicles can improve the safety and efficacy of chemotherapy drugs by facilitating preferential tumor delivery. Polymer-drug conjugates are especially attractive carriers because additional formulation steps are not required during manufacturing, and drug release profiles can be altered based on linker choice. For clinical translation, these vehicles should also be reproducibly and controllably synthesized. Recently, we reported the development of a class of materials called sunflower polymers, synthesized by controlled radical polymerization of hydrophilic petals from a cyclic multimacroinitiator core. This synthesis strategy afforded control over the size of the polymer nanostructures based on their petal polymerization time. In this work, we demonstrate that particle size can be further tuned by varying the degree of polymerization of the cyclic core in addition to that of the petals. Additionally, we investigate the application of these materials for tumor-targeted drug delivery. We demonstrate that folate-targeted, doxorubicin-conjugated sunflower polymers undergo receptor-mediated uptake into cancer cells and pH-triggered drug release leading to cytotoxicity. These materials are attractive as drug carriers due to their discrete and small size, shielded drug cargo that can be triggered for release, and relative ease of synthesis.