Background: Thyroid cancer becomes the most common endocrine cancer with the greatest growing incidence in this decade. Sorafenib is a multikinase inhibitor for the treatment of progressive radioactive iodine-refractory differentiated thyroid cancer (DTC), while the off-target toxicity effect is usually inconvenient for patients taking. 
Methods: In this study, hollow mesoporous silica nanoparticles (HMSNs) with transferrin modification (Tf-HMSNs) were loaded with sorafenib (sora@Tf-HMSNs) to help targeted delivery of sorafenib. Due to the biocompatible Tf shell, Tf-HMSNs exhibited excellent biocompatibility and increased intracellular accumulation, which improved the targeting capability to cancer cells in vitro and in vivo. 
Results: Sora@Tf-HMSNs treatment exhibited the strongest inhibition effect of res-TPC-1 cells and res-BCPAP cells compared with sora@HMSNs and sorafenib groups and induced more cancer cell apoptosis. Finally, Western blot analysis was conducted to check the expression of RAF/MEK/ERK signaling pathway after sorafenib encapsulated Tf-HMSNs treatment. 
Conclusion: Overall, sora@Tf-HMSNs can significantly increase the effective drug concentration in cancer cells and thus enhance the anticancer effect, which are expected to be promising nanocarriers to deliver anticancer drugs for effective and safe therapy for RAI-refractory DTC.
Keywords: sorafenib, RAI-refractory DTC, hollow mesoporous silica nanoparticles, transferrin, RAF/MEK/ERK