4.8 Article

Fluorinated Copolypeptide-Stabilized Microbubbles with Maleimide-Decorated Surfaces as Long-Term Ultrasound Contrast Agents

Journal

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 41, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202209610

Keywords

Block Copolymers; Microbubbles; Peptides; Self-Assembly; Ultrasound Contrast Agents

Funding

  1. National Key R&D Program of China [2020YFA0710700]
  2. National Natural Scientific Foundation of China (NNSFC) Projects [52021002, U19A2094, 52073270]

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Amphiphilic copolypeptides containing fluorinated blocks are synthesized to stabilize gas-filled microbubbles (MBs), improving their stability and enhancing ultrasound imaging performance.
Gas-filled microbubbles (MBs) have been clinically used as ultrasound (US) contrast agents for disease diagnosis and treatment. However, it remains a great challenge to resolve the dilemma of stability and contrast enhancement of MBs. Herein, amphiphilic copolypeptides bearing fluorinated blocks are synthesized to stabilize perfluorocarbon (PFC)-filled MBs, exhibiting unique stability under both long-term storage and US imaging conditions. The fluorinated inner layer reduces the internal Laplace pressure and greatly improves the stability of MBs, which can be further reinforced by crosslinking of the dipropargyl-containing middle blocks. To overcome the suppressed nonlinear oscillation of polymer shells, maleimide groups are introduced onto the surface of MBs, enabling in situ reaction with plasma proteins to enhance second harmonic signals without compromising the stability of MBs, conferring better US imaging performance than that of Sono Vue (TM) MBs.

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