Highly cell-penetrating and ultra-pH-responsive nanoplatform for controlled drug release and enhanced tumor therapy.

A stimuli-triggered drug release strategy could considerably reduce side effects while improving the bioavailability of chemotherapeutics. Here, we report that a series of ultra-pH-responsive copolymers are highly efficient drug delivery systems for near-infrared (NIR) imaging and controlled drug release. These polymers self-assemble into nano-sized micelles due to their amphipathic structure and deliver hydrophobic drugs (maximum drug loading rate ∼10wt%) into tumor cells via a controlled and pH-triggered modality. By altering the proportion of hydrophilic and hydrophobic chains, the drug loading rate and the in vitro drug release efficiency can be regulated. Moreover, the drug-loaded micelles with optimized compositions exhibited excellent antitumor efficacy in HeLa and MCF-7 cells, while the blank micelles had minimal cytotoxicity. Cellular uptake experiments further indicated that the ultra-pH-responsive micelles could be rapidly internalized in the tumor cells. This study demonstrated the strong potential of the ultra-pH-responsive platform as a universal carrier for the delivery of anticancer drugs to maximize their therapeutic effect.