Hybrid nanostructures are promising for ultrasound-triggered drug delivery and treatment, called sonotheranostics. Structures based on plasmonic nanoparticles for photothermal-induced microbubble inflation for ultrasound imaging exist. However, they have limited therapeutic applications because of short microbubble lifetimes and limited contrast. Photochemistry-based sonotheranostics is an attractive alternative, but building near-infrared (NIR)-responsive echogenic nanostructures for deep tissue applications is challenging because photolysis requires high-energy (UV-visible) photons. Here, we report a photochemistry-based echogenic nanoparticle for in situ NIR-controlled ultrasound imaging and ultrasound-mediated drug delivery. Our nanoparticle has an upconversion nanoparticle core and an organic shell carrying gas generator molecules and drugs. The core converts low-energy NIR photons into ultraviolet emission for photolysis of the gas generator. Carbon dioxide gases generated in the tumor-penetrated nanoparticle inflate into microbubbles for sonotheranostics. Using different NIR laser power allows dual-modal upconversion luminescence planar imaging and cross-sectional ultrasonography. Low-frequency (10 MHz) ultrasound stimulated microbubble collapse, releasing drugs deep inside the tumor through cavitation-induced transport. We believe that the photoechogenic inflatable hierarchical nanostructure approach introduced here can have broad applications for image-guided multimodal theranostics.
Bibliographical noteFunding Information:
This work was supported by the grants from the National Research Foundation of Korea (2017M3A9D8029942, 2021R1A2C2005418 and 2020R1A2C3003958), the Korea Health Industry Development Institute (HW20C2104), and KIST intramural program. We thank Ai Lin Chun of Science Storylab for critically reading and editing the manuscript. The work at the Institute for Lasers, Photonics and Biophotonics was supported by funds from the Office of Vice President for Research and Economic Development at the University at Buffalo.
ASJC Scopus subject areas
- Materials Science(all)
- Physics and Astronomy(all)