The design of nanoscale drug delivery systems used for the targeted co-delivery of multiple therapeutic drugs still remains a challenge. However, researchers prepared mitomycin C (MMC) and methotrexate (MTX) loaded DSPE-PEG micelles (MTX-M-MMC) by self-assembly using the dialysis technique, and the MMC-soybean phosphatidylcholine complex was encapsulated in the MTX-functionalized DSPE-PEG micelles. The experiment suggested that MTX-M-MMC coordinate the early active targeting effect with the late synergistic anticancer effect and achieve a multiple-responsive controlled release of both drugs. MMC was released in a pH-dependent manner, while MTX was release in a protease-dependent manner. Apart from that, MTX-M-MMC is capable of co-delivering both drugs to significantly improve the cellular uptake, intracellular delivery, cytotoxicity and apoptosis in vitro and also the tumor accumulation, penetration and anticancer effect in vivo.
The study promoted the development of the targeted coordination cancer chemotherapy with the systematically administrated, orthogonally functionalized and self-assisted nanoscale micelles, and brings about a more simplified, efficient and flexible nanoscale drug delivery system.