Polymer Nanoformulation of Sorafenib and All-Trans Retinoic Acid for Synergistic Inhibition of Thyroid Cancer

Shijie Li; Shujun Dong; Weiguo Xu; Yang Jiang; Zhongmin Li

doi:10.3389/fphar.2019.01676

Polymer Nanoformulation of Sorafenib and All-Trans Retinoic Acid for Synergistic Inhibition of Thyroid Cancer

Front Pharmacol. 2020 Feb 3:10:1676. doi: 10.3389/fphar.2019.01676. eCollection 2019.

Authors

Shijie Li¹, Shujun Dong², Weiguo Xu³, Yang Jiang⁴, Zhongmin Li⁴

Affiliations

¹ Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
² VIP Integrated Department, School and Hospital of Stomatology, Jilin University, Changchun, China.
³ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China.
⁴ Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.

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.

Keywords: all-trans retinoic acid; drug delivery system; polymer micelles; sorafenib; thyroid cancer.