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Title: Biological activity of dendrimer-methylglyoxal complexes for improved therapeutic efficacy against malignant cells
Authors: Ghosh, Srabanti ×
Chakraborty, Prabal
Chakrabarti, Adrita
Ghosh, Manosij
Mandal, Amit
Saha, Partha
Mukherjee, Anita
Acharya, Somobrata
Ray, Manju #
Issue Date: 5-Jan-2016
Publisher: RSC Publishing
Series Title: RSC Advances vol:6 pages:6631-6642
Abstract: The clinical application of methylglyoxal (MG, a normal human metabolite) for cancer therapy is limited by its facile enzymatic degradation. The present investigation aimed at exploring the potential anticancer therapy of methylglyoxal loaded polyamidoamine (PAMAM) dendrimer with different terminal groups (PAMAM/MG). Uniform PAMAM-NH2/MG with an average particle size of 55±5 nm and high encapsulation efficiencies (EE) of 82±2% have been characterized by transmission electron microscopy (TEM) and spectroscopic techniques. Compared to the free MG, a slow release of MG from dendrimer complex was 85±2% after 24 hours, suggesting the potential of dendrimer as a sustained drug delivery system. PAMAM-NH2/MG possesses biocompatibility with no hemolytic activity and highly effective in growth inhibition of mice carcinoma and sarcoma cells. PAMAM-NH2/MG selectively reduced cell viability of Hela cells with IC50 value of 0.4±0.15 μg/mL while more than 90% normal fibroblast cells have been found to be viable at similar dose. Interestingly, even a lower dose of MG (250 times) in PAMAM-NH2/MG can effectively target Hela cells in comparison to free MG. TEM images demonstrated the ultra structural changes of Hela cells after treated with PAMAM-NH2/MG and also confirmed cellular uptake. DNA damage as measured by commet assay was found to be dose dependent for mice carcinoma and sarcoma cells but no such genotoxic response was observed in human lymphocytes, after treatment with PAMAM-NH2/MG. Thus, dendrimer encapsulated MG might be an effective strategy to target the cancer cells and further improvements of surface functionality of dendrimer can be used as a valuable tool for the development of novel therapeutics in nano-oncology.
ISSN: 2046-2069
Publication status: accepted
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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