A robust pH-sensitive unimolecular dendritic nanocarrier that enables targeted anti-cancer drug delivery via GLUT transporters

[Display omitted] •First report on the synthesis of PAMAM-Tryptophan-(N-acetylglucosamine) [PTN].•Conjugating tryptophan to dendrimer significantly enhanced drug loading capacity.•Cytotoxicity of DOX-PTN was significantly higher than DOX-PAMAM.•Pre-treatment with NAG strongly evidenced GLUT transpor...

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Published in:Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2018-11, Vol.171, p.437-444
Main Authors: Kumar, Pramod, Paknikar, Kishore M., Gajbhiye, Virendra
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Breast cancer
Cell Death - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Survival - drug effects
Dendrimers - chemistry
Doxorubicin - chemistry
Doxorubicin - pharmacology
Drug Carriers - chemistry
Drug Delivery Systems
Drug Screening Assays, Antitumor
Glucose Transport Proteins, Facilitative - metabolism
GLUT transporters
Hep G2 Cells
Humans
Hydrogen-Ion Concentration
Liver carcinoma
Models, Molecular
Molecular Structure
N-acetylglucosamine
Nanoparticles - chemistry
PAMAM dendrimer
Particle Size
Surface Properties
Unimolecular nanocarrier
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Summary:[Display omitted] •First report on the synthesis of PAMAM-Tryptophan-(N-acetylglucosamine) [PTN].•Conjugating tryptophan to dendrimer significantly enhanced drug loading capacity.•Cytotoxicity of DOX-PTN was significantly higher than DOX-PAMAM.•Pre-treatment with NAG strongly evidenced GLUT transporters mediated delivery.•Binding NAG is an attractive tactic for GLUT-mediated delivery of anticancer drugs. This study explores the potential of dendritic unimolecular nanoconstruct, PAMAM-Tryptophan-(N-acetylglucosamine) [PTN] as anti-cancer drug delivery system. The PAMAM dendrimers were modified with L-tryptophan and N-acetyl glucosamine (NAG) for higher drug loading and to utilize GLUT transporters, respectively. The nanocarriers were characterized by 1H NMR, DSC, and dynamic light scattering. Effect of doxorubicin (DOX)- loaded PTN was studied on MDA-MB-231 and HepG2 cells by cell viability assay. Further flow cytometry analysis was carried out to assess apoptosis. Pre-treatment with NAG was carried out to keep GLUT transporters continuously engaged and to determine GLUT targeting. Confocal microscopy demonstrated significantly higher uptake of FITC tagged PTN than PAMAM. DOX-loaded PTN demonstrated pH-sensitive drug release with significant (P 
ISSN:0927-7765
1873-4367
DOI:10.1016/j.colsurfb.2018.07.053