Highly uniform ultrasound-sensitive nanospheres produced by a pH-induced micelle-to-vesicle transition for tumor-targeted drug delivery

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.