Ultrasound-targeted microbubble destruction enhances RSL3-induced ferroptosis in anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy with limited effective therapies. Ferroptosis, a form of programmed cell death, is closely associated with thyroid cancer prognosis and represents a potential therapeutic target. This study evaluated the antitumor effects of ultrasound-targeted microbubble (MB) destruction (UTMD)-mediated RAS-selective lethal 3 (RSL3) delivery to induce ferroptosis in ATC. MBs loaded with ferroptosis inducer RSL3 were synthesized and intravenously administered in a nude mouse ATC model, followed by localized ultrasound irradiation to enable targeted intratumoral drug release. RSL3-MBs exhibited uniform particle size, good biocompatibility, and excellent contrast performance. The combination of RSL3-MBs with UTMD significantly inhibited the growth of ATC without evident systemic toxicity. This strategy was shown to be more effective than the delivery methods involving either RSL3 solution or RSL3-MBs alone. These findings support UTMD-mediated RSL3 delivery as an effective approach to enhance ferroptosis-based therapy for ATC.