One-Step Nanosurface Self-Assembly of d-Peptides Renders Bubble-Free Ultrasound Theranostics

The surface bioinspired modification of particles and films is a mainstream direction in biomaterial design and application. The interfacial coating of extracellular-matrix-like hydrogel can endow functional inorganic nanoparticles high circulation stability and biocompatibility but remains challenging due to large surface tension difference between organic gelators and solid nanosurfaces. Herein, the supramolecular hydrogel of NapG_dF_dF_dK around gold nanorods (Au NRs-Gel) has been constructed by the amidation-grafting modification and the protonation-induced interface-assistant assembly of peptide precursors. As a proof of concept study, the acoustic cavitation experiments and in vitro ultrasound imaging have proved that the abundant hydrophobic microdomains as well as the water-rich network in the supramolecular hydrogel can serve as valid sites to efficiently generate and stabilize nanobubbles as cavitation seeds to realize bubble-free ultrasound imaging. In vivo augmented ultrasound imaging and imaging-guided high intensity focused ultrasound (HIFU) therapy based on the Balb/c mice bearing HeLa tumor model have been conducted. As the first example of using nanosurface hydrogelation to endow nanoparticles with bubble-free ultrasound theranostic ability, this work offers a simple approach to design multifunctional nanovehicles for ultrasound-guided drug/protein/gene delivery.