Thailandepsin A-loaded and octreotide-functionalized unimolecular micelles for targeted neuroendocrine cancer therapy.

Autor: Jaskula-Sztul R; Department of Surgery, University of Wisconsin, Madison, WI, 53705, USA., Xu W; Department of Biomedical Engineering and Wisconsin Institutes for Discovery, University of Wisconsin-Madison, 1550 Engineering Drive, 3144 Engineering Centers Building, Madison, WI, 53715, USA., Chen G; Department of Biomedical Engineering and Wisconsin Institutes for Discovery, University of Wisconsin-Madison, 1550 Engineering Drive, 3144 Engineering Centers Building, Madison, WI, 53715, USA; Department of Materials Science and Engineering, University of Wisconsin-Madison, Madison, WI, 53715, USA., Harrison A; Department of Surgery, University of Wisconsin, Madison, WI, 53705, USA., Dammalapati A; Department of Surgery, University of Wisconsin, Madison, WI, 53705, USA., Nair R; Department of Surgery, University of Wisconsin, Madison, WI, 53705, USA., Cheng Y; University of Texas Health Sciences Center San Anto-Division, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA., Gong S; Department of Biomedical Engineering and Wisconsin Institutes for Discovery, University of Wisconsin-Madison, 1550 Engineering Drive, 3144 Engineering Centers Building, Madison, WI, 53715, USA; Department of Materials Science and Engineering, University of Wisconsin-Madison, Madison, WI, 53715, USA. Electronic address: shaoqingong@wisc.edu., Chen H; Department of Surgery, University of Alabama - Birmingham, Birmingham, 1808 7th Avenue South / Suite 502, 35233, AL, USA. Electronic address: herbchen@uab.edu.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2016 Jun; Vol. 91, pp. 1-10. Date of Electronic Publication: 2016 Mar 08.
DOI: 10.1016/j.biomaterials.2016.03.010
Abstrakt: Due to the overexpression of somatostatin receptors in neuroendocrine (NE) cancers, drug nanocarriers conjugated with somatostatin analogs, such as octreotide (OCT), for targeted NE cancer therapy may offer increased therapeutic efficacies and decreased adverse effects. In this study, OCT-functionalized unimolecular micelles were prepared using individual hyperbranched polymer molecules consisting of a hyperbranched polymer core (Boltorn(®) H40) and approximately 25 amphiphilic polylactide-poly(ethlyene glycol) (PLA-PEG) block copolymer arms (H40-PLA-PEG-OCH3/OCT). The resulting micelles, exhibiting a uniform core-shell shape and an average hydrodynamic diameter size of 66 nm, were loaded with thailandepsin-A (TDP-A), a relatively new naturally produced histone deacetylase (HDAC) inhibitor. In vitro studies using flow cytometry and confocal laser scanning microscopy (CLSM) demonstrated that OCT conjugation enhanced the cellular uptake of the unimolecular micelles. Consequently, TDP-A-loaded and OCT-conjugated micelles exhibited the highest cytotoxicity and caused the highest reduction of NE tumor markers. Finally, the in vivo studies on NE cancer bearing nude mice demonstrated that TDP-A-loaded and OCT-conjugated micelles possessed superior anticancer activity in comparison with other TDP-A formulations or drug alone, while showing no detectable systemic toxicity. Thus, these TDP-A-loaded and OCT-conjugated micelles offer a promising approach for targeted NE cancer therapy.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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