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Poly((D,L)lactic-glycolic)acid–star glucose nanoparticles for glucose transporter and hypoglycemia-mediated tumor targeting

Authors Park JH, Cho HJ, Kim DD

Received 29 July 2017

Accepted for publication 9 September 2017

Published 11 October 2017 Volume 2017:12 Pages 7453—7467

DOI https://doi.org/10.2147/IJN.S147668

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Thomas Webster


Ju-Hwan Park,1 Hyun-Jong Cho,2 Dae-Duk Kim1

1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 2College of Pharmacy, Kangwon National University, Chuncheon, Gangwon, Republic of Korea

Abstract: Poly((D,L)lactic-glycolic)acid–star glucose (PLGA-Glc) polymer-based nanoparticles (NPs) were fabricated for tumor-targeted delivery of docetaxel (DCT). NPs with an approximate mean diameter of 241 nm, narrow size distribution, negative zeta potential, and spherical shape were prepared. A sustained drug release pattern from the developed NPs was observed for 13 days. Moreover, drug release from PLGA-Glc NPs at acidic pH (endocytic compartments and tumor regions) was significantly improved compared with that observed at physiological pH (normal tissues and organs). DCT-loaded PLGA-Glc NPs (DCT/PLGA-Glc NPs) exhibited an enhanced antiproliferation efficiency rather than DCT-loaded PLGA NPs (DCT/PLGA NPs) in Hep-2 cells, which can be regarded as glucose transporters (GLUTs)-positive cells, at ≥50 ng/mL DCT concentration range. Under glucose-deprived (hypoglycemic) conditions, the cellular uptake efficiency of the PLGA-Glc NPs was higher in Hep-2 cells compared to that observed in PLGA NPs. Cy5.5-loaded NPs were prepared and injected into a Hep-2 tumor-xenografted mouse model for in vivo near-infrared fluorescence imaging. The PLGA-Glc NPs group exhibited higher fluorescence intensity in the tumor region than the PLGA NPs group. These results imply that the PLGA-Glc NPs have active tumor targeting abilities based on interactions with GLUTs and the hypoglycemic conditions in the tumor region. Therefore, the developed PLGA-Glc NPs may represent a promising tumor-targeted delivery system for anticancer drugs.

Keywords: PLGA-Glc, nanoparticles, glucose transporter, hypoxia, tumor targeting

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