Low-intensity focused ultrasound-assisted dox-piperine amplified therapy on anaplastic thyroid carcinoma by hybird tumor-targeting nanoparticles

Abstract

Therapies against anaplastic thyroid carcinoma (ATC) have been sticking in the predicament of multiple drug resistance (MDR). To address multiple drug resistance and promote therapeutic efficiency, we developed a novel nanoparticle with properties of spatial-temporally controlled release based on poly (amido amine) dendrimers-G4(PAMAM-G4) & Low-intensity focused ultrasound (LIFU) and synergistic killing effect by the combination of Dox and Piperine (PIP). We synthesized a core-shell-structured nanoparticle named [email protected] by thin film hydration-sonoseismic method, where the core was consisted of PAMAM-G4 encapsulating Dox and the shell was formed by IR780-PIP-co-loaded bilayer lipid membrane. The therapeutic efficacy and biosafety of nanoparticles were evaluated by cell experiments and xenograft tumor nude mouse model experiments. Data showed that, with the intervention by LIFU, tumor-targeting dual-drug-loaded nanoparticles termed as [email protected] exhibited superior therapeutic effect over non-tumor-targeting dual-drug-loaded nanoparticles termed as [email protected] and remarkable advantages over non-tumor-targeting Dox-loaded-only nanoparticles termed as PAMAM-Dox, both in vitro and in vivo. With the addition of IR780, [email protected] NPs showed reduced side effects caused by drug-leakage, enhanced tumor-specific therapeutic effects and granted praiseworthy PA imaging capacity. Moreover, [email protected] possesses sound biocompatibility and biosafety. [email protected] has yielded great prospects in future treatment of anaplastic thyroid carcinoma and the potential of visualized therapy.