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.

). These NCs demonstrate excellent effects for photothermal ablation of tumors after intratumoral injection on 4T1 tumor-bearing mice. Our study may provide a facile strategy for the fabrication of multifunctional theranostics towards simultaneous strong CT signal and excellent PTT.

Drug delivery systems (DDSs) have been getting more and more attention in the field of cancer therapy with the development of nanotechnology. But remote and noninvasive controlled drug release for improving treatment efficacy and reducing side effects faces great challenge. We report a kind of "smart" nanocomposites (NCs) that is sensitive to the surrounding temperature by grafting a layer of thermosensitive polymer, poly(N-isopropylacrylamide) (pNIPAm), on the surface of single Cu7S4 nanoparticle (NP) via atomtransfer radical polymerization (ATRP). These NCs demonstrate a photothermal conversion efficiency of 25.4% under 808-nm near infrared (NIR) light irradiation and a drug loading content of 19.4% (drug/total NCs, w/w) with a lower critical solution temperature (LCST) of~38°C. At normal physiological temperature (37°C), only 10.8% of the loaded doxorubicin (DOX) was released at physiological pH value (pH 7.4) within 10 h. In the presence of 808-nm irradiation, due to the temperature increment as a result of photothermal effects, DOX was rapidly released.