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

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.