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

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...

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Bibliographic Details
Published in:International journal of nanomedicine 2017-01, Vol.12, p.7453-7467
Main Authors: Park, Ju-Hwan, Cho, Hyun-Jong, Kim, Dae-Duk
Format: Article
Language:English
Subjects:
Acids
Cancer therapies
Chromatography
Drug delivery systems
glucose transporter
Hypoglycemia
Hypoxia
Molecular weight
Nanoparticles
Original Research
Permeability
Pharmacy
PLGA-Glc
tumor targeting
Tumors
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Summary: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.
ISSN:1178-2013
1176-9114
1178-2013
DOI:10.2147/IJN.S147668