Abstract
Part of differentiated thyroid cancer will relapse or develop into dedifferentiated thyroid cancer after standard therapy, such as surgery or radionuclide therapy. Sorafenib (SOR) is recommended for the treatment of advanced or radioiodine-refractory thyroid cancer. The monotherapy using SOR is often hampered by its modest efficacy, serve systemic toxicity, and high occurrence of drug resistance. In order to enhance the antitumor effect of SOR and reduce its side effects, SOR and all-trans retinoic acid (ATRA), a differentiation-promoting drug, were loaded into poly(ethylene glycol)–poly(lactide-co-glycolide) (PEG–PLGA) polymer micelles in this study. The drug-loaded micelles, PM/(SOR+ATRA), exhibited relatively slow drug release and effective cell uptake. Compared with other treatment groups, the PM/(SOR+ATRA) treatment group showed the most significant antitumor effect and minimal systemic toxicity toward the FTC-133 thyroid cancer-bearing BALB/c nude mouse model. Immunofluorescence analysis confirmed that PM/(SOR+ATRA) could significantly promote apoptosis and re-differentiation of tumor cells. All the results demonstrated that polymer micelles loaded with SOR and ATRA could treat thyroid cancer more effectively and safely.
Highlights
As the most common endocrine malignancy, thyroid cancer has become more and more prevalent in recent years (James et al, 2018)
The results demonstrated that all-trans retinoic acid (ATRA) significantly enhanced the antitumor efficiency of SOR against FTC-133 tumor cells in vitro and in vivo, and PEG–PLGA coloaded with SOR and ATRA showed the most obvious tumor inhibition effect
PEG–PLGA copolymers were fabricated through the ring-opening polymerization (ROP) of lactide and glycolide with PEG or tetrahydroxyl-functionalized PEG serving as the initiator and Sn(Oct)2 serving as the catalyst
Summary
As the most common endocrine malignancy, thyroid cancer has become more and more prevalent in recent years (James et al, 2018). Differentiated thyroid cancer (DTC), which originates from follicular epithelial cells, accounts for more than 95% of thyroid cancer and usually has a good prognosis (Cabanillas et al, 2016). Surgery and postoperative thyrotropin suppression therapy or radionuclide therapy (I131) are currently the standard treatment for DTC (Haugen et al, 2016). Approximately 30% of these patients will relapse after the standard treatment (Kim et al, 2018b). The recurrent DTC tends to lose the ability to absorb iodine, thereby losing the option of radioactive iodine therapy. Multi-targeted kinase inhibitors such as sorafenib (SOR) are the firstline treatment of radioiodine-refractory DTC (RAIR-DTC) or advanced thyroid cancer, and they
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