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

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 < 0.001) higher cytotoxicity against breast cancer cells than PAMAM. The percentage viability after 48 h was found to be 5.0 ± 2.32, 18.3 ± 2.91 and 5.9 ± 0.55% for free DOX, PAMAM-DOX, and PTN-DOX, respectively in MDA-MB-231 cells. A similar profile was observed for HepG2 cells. Further, flow cytometry analysis confirmed that the cell death mode was apoptosis. Pre-treatment with NAG during cell viability assay and flow cytometry evidenced GLUT targeting. Taken together, conjugating tryptophan to parent dendrimer could significantly enhance cargo loading capacity and binding NAG could be an attractive therapeuti...
Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research