Significance – Current therapies have shown limited success in improving outcomes for lethal anaplastic thyroid cancer (ATC) characterized by rapid tumor growth and metastatic dissemination caused by the activation of genetic mutations. RNAi nanotechnology is emerging as a promising strategy for effectively treating such cancers and suppressing metastasis. However, suboptimal systemic delivery of RNAi agents to tumors and variable therapeutic responses because of tumor heterogeneity represent challenging hurdles to widespread clinical use. We describe an innovative near-infrared nanoplatform for systemic delivery of siRNA to ATC and real-time tracking of tumor accumulation. Antitumor growth and antimetastasis effects in an orthotopic ATC mouse model suggest this nanoplatform as a valuable tool for personalized treatment of ATC and other advanced malignancies.

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