Title

N-acetyl-D-glucosamine-conjugated PAMAM dendrimers as dual receptor-targeting nanocarriers for anticancer drug delivery

RIS ID

144781

Publication Details

Pooja, D., Srinivasa, T., Kulhari, H., Kadari, A., Adams, D. J., Bansal, V. & Sistla, R. (2020). N-acetyl-D-glucosamine-conjugated PAMAM dendrimers as dual receptor-targeting nanocarriers for anticancer drug delivery. European Journal of Pharmaceutics and Biopharmaceutics, 154 377-386.

Abstract

N-acetyl-D-glucosamine-labelled dendrimers (NAG-Dend) were synthesized for the targeted delivery of camptothecin (CPT) to A549 human lung adenocarcinoma cells, which overexpress glucose transporters and lectin receptors. CPT loaded, NAG-Dend (NAG-Dend-CPT) exhibited more rapid and higher cellular uptake than the unlabelled dendrimer formulation (Dend-CPT), leading to enhanced cytotoxicity. Compared with native CPT, NAG-Dend-CPT was 4.5 times more toxic to A549 cells. The anticancer activity of the different CPT formulations was dose and time dependent. NAG-Dend-CPT also increased reactive oxygen species generation, induced higher apoptosis and showed greater inhibition of A549 cell migration than Dend-CPT. The selective accumulation of NAG-Dend in the lungs of tumour-bearing mice confirmed that the NAG-based dendrimer system can target lung metastasis tumours in a biological system. Overall, our results show that NAG-conjugated dendrimers could be a promising nanocarrier system for the delivery of anticancer drugs, including CPT, to human lung cancer cells.

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Link to publisher version (DOI)

http://dx.doi.org/10.1016/j.ejpb.2020.07.020