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
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2017
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Acceso en línea:https://doaj.org/article/48c0a443f1d444128593fc1263ffb3f5
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Sumario: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