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Highly uniform ultrasound-sensitive nanospheres produced by a pH-induced micelle-to-vesicle transition for tumor-targeted drug delivery
Authors:Yiru Wang  Tinghui Yin  Zhenwei Su  Chen Qiu  Yong Wang  Rongqin Zheng  Meiwan Chen  Xintao Shuai
Affiliation:1.Guangdong Provincial Key Lab of Liver Disease and Department of Medical Ultrasonics,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,China;2.PCFM Lab of Ministry of Education, School of Materials Science and Engineering,Sun Yat-sen University,Guangzhou,China;3.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences,University of Macau,Macau,China
Abstract:Although gas-filled microbubbles with high echogenicity are widely applied inclinical 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 apH-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.
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