Low intensity focused ultrasound (LIFU) triggered drug release from cetuximab-conjugated phase-changeable nanoparticles for precision theranostics against anaplastic thyroid carcinoma
- 25 October 2018
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Biomaterials Science
- Vol. 7 (1), 196-210
- https://doi.org/10.1039/c8bm00970h
Abstract
Currently, multifunctional nanotechnology is strongly expected to improve the prospect of treatment and diagnosis. In this study, we synthesized epidermal growth factor (EGFR)-targeted phase-changeable polymer nanoparticles (C-HPNs) loaded with two drugs (C225 and 10-HCPT) for specific tumor targeting, synergistic chemotherapy, and ultrasound imaging under low-intensity focused ultrasound (LIFU). Cetuximab (C225), an EGFR-targeted monoclonal antibody, was conjugated on the surface of the nanoparticles, leading to a significantly high binding affinity to EGFR-overexpressing anaplastic thyroid C643 cells both in vitro and in vivo. As expected, an increase of more than 3- to 4-fold in the release rates of 10-HCPT was observed after LIFU irradiation in vitro, demonstrating that LIFU could enhance the release of drugs from the nanoparticles. Combined treatment with C-HPNs and LIFU showed excellent inhibition of cell proliferation in vitro, as well as a remarkable therapeutic effect in vivo. Moreover, the combined treatment simultaneously enhanced ultrasound imaging by LIFU-induced acoustic droplet vaporization (ADV). In conclusion, C225-modified and phase-changeable nanoparticles combined with LIFU exhibited great promise for concurrent targeted ultrasound molecular imaging and effective synergistic antitumor therapy.Keywords
Funding Information
- National Natural Science Foundation of China (31630026, 81630047, 81471713)
- Ministry of Science and Technology of the People's Republic of China (3R216P843430)
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