Cellular uptake of polyurethane nanocarriers mediated by gemini quaternary ammonium

The effective passage of drug formulations into tumor cells is a key factor in the development of nanoscale delivery systems. However, rapid cellular uptake with reduced toxicity remains a great challenge for efficient and safe delivery. In this study, we first use gemini quaternary ammonium (GQA) as a cell internalization promoter to enhance the cellular uptake of drug nanocarriers. It is found that a twenty times faster cell internalization could be achieved by introducing GQA into biodegradable multiblock polyurethane nanomicelles, as confirmed by flow cytometry and confocal laser scanning microscopy (CLSM) studies. Meanwhile, an added methoxyl-poly(ethylene glycol) (mPEG) outer corona could protect these cationic micelles from cytotoxicity at high concentrations, as verified by methyl tetrazolium (MTT) assay. Moreover, GQA not only acts as an enhancer for rapid cellular entry, but also plays an important role in controlled self-assembly and high drug loading capacity. Our work offers a new understanding on the role of cationic surfactants; and provides a facile and economical approach for the design of versatile drug nanocarriers to achieve efficient delivery and good biocompatibility.