Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy.

Autor: Li L; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China., Di X; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China., Wu M; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China., Sun Z; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China., Zhong L; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China., Wang Y; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China., Fu Q; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China., Kan Q; Department of Pharmacology, Shenyang Pharmaceutical University, China., Sun J; Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, China. Electronic address: sunjin66@21cn.com., He Z; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Jazyk: angličtina
Zdroj: Nanomedicine : nanotechnology, biology, and medicine [Nanomedicine] 2017 Apr; Vol. 13 (3), pp. 987-998. Date of Electronic Publication: 2016 Nov 25.
DOI: 10.1016/j.nano.2016.11.012
Abstrakt: Designing active targeting nanocarriers with increased cellular accumulation of chemotherapeutic agents is a promising strategy in cancer therapy. Herein, we report a novel active targeting strategy based on the large amino acid transporter 1 (LAT1) overexpressed in a variety of cancers. Glutamate was conjugated to polyoxyethylene stearate as a targeting ligand to achieve LAT1-targeting PLGA nanoparticles. The targeting efficiency of nanoparticles was investigated in HeLa and MCF-7 cells. Significant increase in cellular uptake and cytotoxicity was observed in LAT1-targeting nanoparticles compared to the unmodified ones. More interestingly, the internalized LAT1 together with targeting nanoparticles could recycle back to the cell membrane within 3 h, guaranteeing sufficient transporters on cell membrane for continuous cellular uptake. The LAT1 targeting nanoparticles exhibited better tumor accumulation and antitumor effects. These results suggested that the overexpressed LAT1 on cancer cells holds a great potential to be a high-efficiency target for the rational design of active-targeting nanosystems.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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