Targeted therapy of highly aggressive thyroid papillary carcinoma by AS1411-guided nanomaterials.

AIMS: Aggressive papillary thyroid carcinoma (PTC) is often refractory to radioiodine therapy, and effective targeted therapeutic strategies are urgently needed. This study aimed to construct an AS1411 aptamer-guided gold nanoparticle drug delivery system loaded with doxorubicin (AS1411/AuNPs/Dox) for targeted synergistic therapy of PTC.

MATERIALS AND

METHODS

The nanoplatform was synthesized and characterized by transmission electron microscopy, dynamic light scattering and Ultraviolet-Visible (UV-Vis) spectrometry. In vitro cellular uptake, cytotoxicity and drug release assays were performed, and in vivo antitumor efficacy and biosafety were evaluated in TPC-1 xenograft mouse models.

RESULTS

The AS1411/AuNPs/Dox system exhibited good monodispersity, stability and dual pH/near-infrared (NIR) responsive doxorubicin release. AS1411-mediated targeting enabled selective enrichment and enhanced cytotoxicity in nucleolin-high TPC-1 cells. Combined chemo-photothermal therapy significantly suppressed tumor growth in vivo with no obvious systemic toxicity, and the antitumor effect was associated with regulation of mitochondrial apoptosis-related genes.

CONCLUSIONS

This multifunctional targeted nanoplatform exerts potent synergistic antitumor efficacy against aggressive PTC with good biosafety, providing a promising novel therapeutic strategy for radioiodine-refractory PTC.