Bifunctional alginate/chitosan stabilized perfluorohexane nanodroplets as smart vehicles for ultrasound and pH responsive delivery of anticancer agents

The combination of ultrasound and chemotherapy has been proposed as a promising strategy to achieve a better anticancer therapeutic efficacy. Here we present a facile strategy to construct novel bifunctional nanodroplets as smart vehicles for ultrasound and pH responsive delivery of anticancer agents. PFH is used as core and chitosan/alginate complexes are used as the stable shells of the nanodroplets. The effects of alginate/chitosan ratio, and the amount of surfactant as well as PFH on the size, size distribution, and encapsulation efficiency of nanodroplets are systematically investigated with the optimized formulation identified. The release of the encapsulated doxorubicin hydrochloride can be triggered by changing the pH value of the surrounding environment and the exposure to ultrasound. The nanodroplets also show strong ultrasound contrast via droplet-to-bubble transition as demonstrated by B-mode ultrasound imaging. The hemolytic activity and cytotoxicity are further studied, revealing the biocompatibility of the nanodroplets. The in vivo antitumor results demonstrate that the prepared droplets show excellent antitumor therapeutic efficacy and outstanding tumor-targeting ability. The proposed alginate/chitosan stabilized PFH nanodroplets represent an important advance in fabricating multifunctional therapeutic materials with great promises in the applications of combined antitumor therapies.