Biocompatible Chitosan Nanobubbles for Ultrasound-Mediated Targeted Delivery of Doxorubicin

Ultrasound-targeted delivery of nanobubbles (NBs) has become a promising strategy for noninvasive drug delivery. The biosafety and drug-transporting ability of NBs have been a research hotspot, especially regarding chitosan NBs due to their biocompatibility and high biosafety. Since the drug-carrying capacity of chitosan NBs and the performance of ultrasound-assisted drug delivery remain unclear, the aim of this study was to synthesize doxorubicin hydrochloride (DOX)-loaded biocompatible chitosan NBs and assess their drug delivery capacity. In this study, the size distribution of chitosan NBs was measured by dynamic light scattering, while their drug-loading capacity and ultrasound-mediated DOX release were determined by a UV spectrophotometer. In addition, a clinical ultrasound imaging system was used to evaluate the ability of chitosan NBs to achieve imaging enhancement, while the biosafety profile of free chitosan NBs was evaluated by a cytotoxicity assay in MCF-7 cells. Furthermore, NB-mediated DOX uptake and the apoptosis of Michigan Cancer Foundation-7 (MCF-7) cells were measured by flow cytometry. The results showed that the DOX-loaded NBs (DOX-NBs) exhibited excellent drug-loading ability as well as the ability to achieve ultrasound enhancement. Ultrasound (US) irradiation promoted the release of DOX from DOX-NBs in vitro. Furthermore, DOX-NBs effectively delivered DOX into mammalian cancer cells. In conclusion, biocompatible chitosan NBs are suitable for ultrasound-targeted DOX delivery and are thus a promising strategy for noninvasive and targeted drug delivery worthy of further investigation.