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Nanocapsule-based targeted delivery and stimulus-responsive release can increase drug effectiveness, while reducing the side effects of the drug. However, difficulties in the scale-up synthesis, fast burst release, and low degradability, could hamper the translation of drug nanocapsules from lab to clinic. Here we have controllably functionalized the biodegradable and widely available polysuccinimide, in order to obtain an amphiphilic poly(amino acid). Using this polymer, we designed nanocapsules (< 100 nm) for hydrophobic drug delivery, which could facilitate tumor targeting, hydrogen bond-based pH-responsive release, and real-time fluorescence tracking, in the second near-infrared region. This method is versatile, eco-friendly, and easy to scale up at low costs. In addition, this system can carry a cocktail of drugs, obtained by loading multiple anticancer drugs to the same vehicle. Our nanocapsules were observed to be stable in blood vessels (pH = 7.4), and the pH-responsive release (pH = 5.0 in lysosome) was sustained. The chemotherapy results in tumor-xenografted mice suggested that our nanocapsule was safe and efficient, and may be a useful tool for drug delivery.
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