Redox-responsive carrier based on fluorinated gemini amphiphilic polymer for combinational cancer therapy

Polymeric micelle has emerged as an efficient implement to overcome the shortcomings of conventional cancer chemotherapy due to its superior solubility of hydrophobic drugs and less side effects of drugs. However, insufficient dilution resistance and ordinary therapeutic effect severely restrict the further translation of current drug-loaded polymeric micelles. Here, we showed that well-defined G-Fn (n = 5, 9, 13) polymeric micelles possessed excellent capabilities as a drug carrier in light of high drug loading content, high stability and precise drug release combined with wonderful endocytosis efficiency to tumors. The representative G-F13 exhibited an excellent dilution resistance, outstanding high drug loading content (22 wt%) and drug loading efficiency (82%), which might be attributed to the extremely low critical micelle concentration conferred by its special Gemini structure and the superhydrophobicity of the fluorocarbon chain. Furthermore, the cross-linked internal fluoride membrane consisted of the two chains of the Gemini structure made G-F13 stable even after 24 h of incubation in 10% fetal bovine serum (FBS). The camptothecin (CPT) release was selectively triggered by glutathione (GSH) and H2O2, reaching 75% and 85% after 24 h respectively, in which only 15% of drugs leak under physiological conditions. The CCK-8 assays of Hela cells showed that CPT-loaded G-F13 micelles had high cell compatibility (200 mu g/mL, 93% cell viability, 48 h) and high cancer cytotoxicity (IC50 0.1 mu g/mL). Notably, a tenfold lower dosage of loaded CPT had an higher tumor growth inhibition than the free CPT. This result was attributed to the combined treatment of fluorinated drug carriers were more likely to penetrate the cell membrane to enter tumor cells, the cytotoxicity of selenic acid generated after the oxidation of G-F13 and the large amounts of CPT after redox release. Excellent physical and chemical properties as well as good therapeutic effects reveal that G-F13 can act as a promising drug carrier to widely use in cancer chemotherapy.

Automated summary

The well-defined G-Fn polymeric micelles (n = 5, 9, 13) showed high drug loading content, stability, and precise drug release, making them promising drug carriers for cancer chemotherapy. They exhibited excellent dilution resistance and significant tumor cell cytotoxicity, providing a potential solution to the shortcomings of conventional chemotherapy.