SCHEDULED MAINTENANCE
Tumor-targeted co-delivery of mitomycin C and 10-hydroxycamptothecin via micellar nanocarriers for enhanced anticancer efficacy†
Abstract
Lipophilicity enhancement of mitomycin C (MMC) was achieved by the introduction of soybean phosphatidyhlcholine (SPC, a kind of phospholipid) (Molecular Pharmaceutics, 2013, 10, 90–101). In addition, the co-delivery of both drugs with one kind of nanoscale drug carrier provided a promising strategy to realize synergistic therapeutic effects and overcome drug resistance in cancer therapy. In this work, we developed folate (FA) functionalized MMC–SPC phospholipid complexes and 10-hydroxycamptothecin (HCPT)-loaded micelles (MMC/HCPT loaded FA-micelles) by film hydration followed by a dialysis and extrusion technique. The MMC/HCPT loaded FA-micelles possessed a nanoscale particle size, a well-controllable drug loading efficiency, and simultaneously sustained and pH-dependent drug release. In vitro cellular uptake analysis suggested that the MMC/HCPT loaded FA-micelles could be efficiently taken up by cancer cells via FA receptor-mediated endocytosis. In vitro cell viability studies demonstrated that the MMC/HCPT loaded FA-micelles showed time- and concentration-dependent cytotoxicity, and significantly enhanced the cytotoxicity compared to both free drugs. Moreover, the MMC/HCPT loaded FA-micelles can simultaneously deliver both MMC and HCPT to not only efficiently promote their accumulation in the tumor as a result of passive and active targeting, but also sufficiently inhibit the tumor growth compared to treatment with both free drugs while reducing the toxicity. The both MMC and HCPT anticancer drug-loaded FA-micelles can be considered as effective therapeutic systems for targeted drug co-delivery and combination cancer chemotherapy.
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