title: AB3-Loaded and Tumor-Targeted Unimolecular Micelles for Medullary Thyroid Cancer Treatment.
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 proliferationin vitro. However, its poor aqueous solubility and stability, fast clearance, and lack of tumor targeting ability limit itsin vivoapplication. 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 vitrocellular 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 expressionin vitro. Furthermore, AB3-loaded, KE108-conjugated micelles demonstrated the best anticancer efficacyin vivowithout any apparent systemic toxicity, thereby offering a promising approach for targeted MTC therapy.
authors.affiliation: Department of Surgery, School of Medicine University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Renata
authors.initials: R
authors.lastname: Jaskula-Sztul
authors.affiliation: Department of Materials Science and Engineering, University of Wisconsin-Madison, Madison, WI 53715, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.
authors.forename: Guojun
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Ajitha
authors.initials: A
authors.lastname: Dammalapati
authors.affiliation: Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: April
authors.initials: A
authors.lastname: Harrison
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Weiping
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Materials Science and Engineering, University of Wisconsin-Madison, Madison, WI 53715, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Shaoqin
authors.initials: S
authors.lastname: Gong
authors.affiliation: Department of Surgery, School of Medicine University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Herbert
authors.initials: H
authors.lastname: Chen
keywords: HDAC inhibitor; KE108; Medullary thyroid cancer; somatostatin receptor; targeted drug delivery; unimolecular micelles