Targeted near infrared hyperthermia combined with immune stimulation for optimized therapeutic efficacy in thyroid cancer treatment
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Le Zhou1, Mengchao Zhang2, Qingfeng Fu1, Jingting Li1, Hui Sun1
1Department of Thyroid Surgery, China-Japan Union Hospital, Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun 130033, China
2Radiology Department, China-Japan Union Hospital, Jilin University, Changchun 130033, China
Hui Sun, e-mail: [email protected]
Keywords: IR820, amino-glucose, near infrared hyperthermia, tumor targeting, heat shock protein 70
Received: June 18, 2015 Accepted: December 29, 2015 Published: January 12, 2016
Treatment of thyroid cancer has incurred much focus because of its high prevalency. As a new strategy treating thyroid cancer, hyperthermia takes several advantages compared with surgery or chemotherapy, including minimal invasion, low systematic toxicity and the ability to enhance the immunogenicity of cancer cells with the expression Hsp70 which serves as Toll-like receptors-4 (TLR-4 agonist). However, Hsp70 as a molecular chaperone can protect cells from heat induced apoptosis and therefore compromise the tumor killing effect of hyperthermia. In this study, to solve this problem, a combined hyperthermia therapy was employed to treat thyroid cancer. We prepared a probe with the tumor targeting agent AG to monitor thyroid tumor issue and generate heat to kill tumor cells in vivo. At the same time Quercetin (inhibitor of HSP70) and lipopolysaccharide (LPS) (agonist of TLR-4) were used for the combined hyperthermia therapy. The results showed that compared with free IR820, AG modification facilitated much enhanced cellular uptake and greatly pronounced tumor targeting ability. The combined therapy exhibited the most remarkable tumor inhibition compared with the single treatments both in vitro and in vivo. These findings verified that the new therapeutic combination could significantly improve the effect of hyperthermia and shed light on a novel clinical strategy in thyroid cancer treatment.
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