Ultrasound-mediated nanobubble destruction (UMND) facilitates the delivery of VEGFR2-targeted CD-TK-loaded cationic nanobubbles in the treatment of bladder cancer

摘要

Background The CD-TK double suicide gene has become an effective therapy for bladder cancer. A novel molecular-targeted ultrasound (US) method has been developed to precisely guide nanobubbles loaded with this gene to regions within bladder tumor cells and is widely used due to its efficiency in delivering drugs to the target tumor. Methods Uniform nanoscaled nanobubbles loaded with CD-TK double suicide gene were developed using a thin-film hydration sonication, carbodiimide chemistry approaches, and electrostatic adsorption methods. Results In the present study, we synthesized CD-TK double suicide gene-loaded cationic nanobubbles conjugated with anti-VEGFR2 that can bind with VEGFR2-positive cells. Fluorescence and flow cytometry evidence show that CD-TK double suicide gene-loaded nanobubbles were successfully developed. CD-TK-CNBs delivered via US-mediated nanobubble destruction (UMND) enhanced transfection efficiency, overexpression of CD-TK double suicide gene, and tumor cell apoptosis, and inhibited tumor cell growth in vitro. Conclusions These CD-TK-CNBs may become a novel treatment for bladder cancer.