Low intensity focused ultrasound (LIFU) triggered drug release from cetuximab-conjugated phase-changeable nanoparticles for precision theranostics against anaplastic thyroid carcinoma

摘要

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.