摘要
Although gas-filled microbubbles with high echogenicity are widely applied in clinical ultrasonography, the micron scale particle size impedes their use in the treatment of solid tumors, which are accessible to objects less than several hundred nanometers. We herein propose an unusual approach involving a pH-induced core-shell micelle-to-vesicle transition to prepare ultrasound-sensitive polymeric nanospheres （polymersomes in structure） possessing multiple features, including nanosize, monodispersity, and incorporation of a phase- transitional imaging agent into the aqueous lumen. These features are not achievable via the conventional double-emulsion method for polymersome preparation. The nanospheres were constructed based on a novel triblock copolymer with dual pH sensitivity. The liquid-to-gas phase transition of the imaging agent induced by external low-frequency ultrasound may destroy the nanospheres for a rapid drug release, with simultaneous tissue-penetrating drug delivery inside a tumor. These effects may provide new opportunities for the development of an effective cancer therapy with few adverse effects.
Although gas-filled microbubbles with high echogenicity are widely applied in clinical ultrasonography, the micron scale particle size impedes their use in the treatment of solid tumors, which are accessible to objects less than several hundred nanometers. We herein propose an unusual approach involving a pH-induced core-shell micelle-to-vesicle transition to prepare ultrasound-sensitive polymeric nanospheres （polymersomes in structure） possessing multiple features, including nanosize, monodispersity, and incorporation of a phase- transitional imaging agent into the aqueous lumen. These features are not achievable via the conventional double-emulsion method for polymersome preparation. The nanospheres were constructed based on a novel triblock copolymer with dual pH sensitivity. The liquid-to-gas phase transition of the imaging agent induced by external low-frequency ultrasound may destroy the nanospheres for a rapid drug release, with simultaneous tissue-penetrating drug delivery inside a tumor. These effects may provide new opportunities for the development of an effective cancer therapy with few adverse effects.
基金
This work was supported by the National Basic Research Program of China （No. 2015CB755500）, the National Natural Science Foundation of China （Nos. U1401242, 51225305, and 81430038）, the Natural Science Foundation of the Guangdong Province （No. 2014A030312018）, the Guangdong Innovative and Entrepreneurial Research Team Program （No. 2013S086）, and the Macao Science and Technology Development Fund （No. 096/2015/A3）.
