Sunflower Polymers for Folate-Mediated Drug Delivery

Abstract

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.

Fabrication of Thermosensitive Cyclic Brush Copolymer with Enhanced Therapeutic Efficacy for Anticancer Drug Delivery

“…Third, cyclic polymer, c ‐PHEMA, was synthesized by the intrachain click cyclization as reported previously . In a typical procedure, 750 mL of DMF was degassed by nitrogen flow for 1 h at 100 °C.…”

Folate‐appended cyclodextrin carrier targets ovarian cancer cells expressing the proton‐coupled folate transporter

“…Importantly, FRα expression in normal tissues is restricted to the luminal side of tissues such as kidney and lung, and, except in kidneys, FRα is not exposed to folate in the circulatory system 11,12. Therefore, to target FRα‐positive cancers, many types of folate‐conjugated drugs and antifolates have been developed in addition to CyD 7,13‐16. However, few studies have examined the dependence of those drugs on folate transporters other than FRα 16…”

Exploiting topology-directed nanoparticle disassembly for triggered drug delivery

“…Nevertheless, polymers with a cyclic topology have shown great promise as potential drug and gene delivery vehicles, often exhibiting greater efficacy, e.g. higher gene transfection efficiencies, [9][10] longer in vivo circulation times, 11 and higher cancer cell uptake, [11][12][13] than their linear counterparts. Furthermore, amphiphilic cyclic polymers display markedly different selfassembly behavior compared to linear amphiphilic polymers, 6 with cyclization shown to affect the dimensions, 14 morphology, [15][16][17] temperature and salt tolerance, [18][19] and degradation 14 of polymer self-assemblies.…”