Folate receptor‐targeted aminoglycoside‐derived polymers for transgene expression in cancer cells

Targeted delivery of anticancer therapeutics can potentially overcome the limitations associated with current chemotherapeutic regimens. Folate receptors are overexpressed in several cancers, including ovarian, triple-negative breast and bladder cancers, making them attractive for targeted delivery of nucleic acid therapeutics to these tumors. This work describes the synthesis, characterization and evaluation of folic acid-conjugated, aminoglycoside-derived polymers for targeted delivery of transgenes to breast and bladder cancer cell lines. Transgene expression was significantly higher with FA-conjugated aminoglycoside-derived polymers than with Lipofectamine, and these polymers demonstrated minimal cytotoxicty. Competitive inhibition using free folic acid significantly reduced transgene expression efficacy of folate-targeted polymers, suggesting a role for folate receptor-mediated uptake. High efficacy FA-targeted polymers were employed to deliver a plasmid expressing the TRAIL protein, which induced death in cancer cells. These results indicate that FA-conjugated aminoglycoside-derived polymers are promising for targeted delivery of nucleic acids to cancer cells that overexpress folate receptors.