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Issue 1, 2017

AB3-loaded and tumor-targeted unimolecular micelles for medullary thyroid cancer treatment

Author affiliations

Abstract

Medullary thyroid cancer (MTC) is often resistant to standard therapies, emphasizing the need for the development of other treatments. A new histone deacetylase inhibitor, AB3, can effectively inhibit MTC cell proliferation in vitro. However, its poor aqueous solubility and stability, fast clearance, and lack of tumor targeting ability limit its in vivo application. Therefore, multifunctional unimolecular micelles were developed for targeted delivery of AB3 for MTC therapy. The unimolecular micelles exhibited a spherical core–shell structure, uniform size distribution, and excellent stability. AB3 was encapsulated into the hydrophobic core of the unimolecular micelles, thus significantly enhancing its aqueous solubility and stability. KE108, a somatostatin analog possessing high affinity to all five subtypes of SSTR, was used as an MTC-targeting ligand. In vitro cellular uptake analyses demonstrated that the KE108 exhibited superior targeting ability in MTC cells compared to octreotide, the first clinically used somatostatin analog. Moreover, the AB3-loaded and KE108-conjugated unimolecular micelles exhibited the best efficacy in suppressing MTC cell growth and tumor marker expression in vitro. Furthermore, AB3-loaded, KE108-conjugated micelles demonstrated the best anticancer efficacy in vivo without any apparent systemic toxicity, thereby offering a promising approach for targeted MTC therapy.

Graphical abstract: AB3-loaded and tumor-targeted unimolecular micelles for medullary thyroid cancer treatment

Supplementary files

Article information


Submitted
28 Sep 2016
Accepted
17 Nov 2016
First published
02 Dec 2016

J. Mater. Chem. B, 2017,5, 151-159
Article type
Paper

AB3-loaded and tumor-targeted unimolecular micelles for medullary thyroid cancer treatment

R. Jaskula-Sztul, G. Chen, A. Dammalapati, A. Harrison, W. Tang, S. Gong and H. Chen, J. Mater. Chem. B, 2017, 5, 151 DOI: 10.1039/C6TB02530G

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