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

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 glu...

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Autores principales: Park JH, Cho HJ, Kim DD
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:48c0a443f1d444128593fc1263ffb3f52021-12-02T04:23:13ZPoly((D,L)lactic-glycolic)acid–star glucose nanoparticles for glucose transporter and hypoglycemia-mediated tumor targeting1178-2013https://doaj.org/article/48c0a443f1d444128593fc1263ffb3f52017-10-01T00:00:00Zhttps://www.dovepress.com/polydllactic-glycolicacid-star-glucose-nanoparticles-for-glucose-trans-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ju-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 targetingPark JHCho HJKim DDDove Medical PressarticlePLGA-Glcnanoparticlesglucose transporterhypoxiatumor targetingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 7453-7467 (2017)
institution DOAJ
collection DOAJ
language EN
topic PLGA-Glc
nanoparticles
glucose transporter
hypoxia
tumor targeting
Medicine (General)
R5-920
spellingShingle PLGA-Glc
nanoparticles
glucose transporter
hypoxia
tumor targeting
Medicine (General)
R5-920
Park JH
Cho HJ
Kim DD
Poly((D,L)lactic-glycolic)acid–star glucose nanoparticles for glucose transporter and hypoglycemia-mediated tumor targeting
description 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
format article
author Park JH
Cho HJ
Kim DD
author_facet Park JH
Cho HJ
Kim DD
author_sort Park JH
title Poly((D,L)lactic-glycolic)acid–star glucose nanoparticles for glucose transporter and hypoglycemia-mediated tumor targeting
title_short Poly((D,L)lactic-glycolic)acid–star glucose nanoparticles for glucose transporter and hypoglycemia-mediated tumor targeting
title_full Poly((D,L)lactic-glycolic)acid–star glucose nanoparticles for glucose transporter and hypoglycemia-mediated tumor targeting
title_fullStr Poly((D,L)lactic-glycolic)acid–star glucose nanoparticles for glucose transporter and hypoglycemia-mediated tumor targeting
title_full_unstemmed Poly((D,L)lactic-glycolic)acid–star glucose nanoparticles for glucose transporter and hypoglycemia-mediated tumor targeting
title_sort poly((d,l)lactic-glycolic)acid–star glucose nanoparticles for glucose transporter and hypoglycemia-mediated tumor targeting
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/48c0a443f1d444128593fc1263ffb3f5
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AT chohj polydllacticglycolicacidndashstarglucosenanoparticlesforglucosetransporterandhypoglycemiamediatedtumortargeting
AT kimdd polydllacticglycolicacidndashstarglucosenanoparticlesforglucosetransporterandhypoglycemiamediatedtumortargeting
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