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Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells

Authors Gu, Cheng J, Jin, Cheng SH, Wong

Published 17 November 2011 Volume 2011:6 Pages 2889—2898

DOI https://doi.org/10.2147/IJN.S25162

Review by Single-blind

Peer reviewer comments 4

Yan-Juan Gu1,2,*, Jinping Cheng2,*, Jiefu Jin3, Shuk Han Cheng2, Wing-Tak Wong1
1Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, 2Department of Biology and Chemistry, The City University of Hong Kong, 3Department of Chemistry, The University of Hong Kong, Hong Kong, China
*These authors contributed equally to this work

Abstract: Single-walled carbon nanotubes (SWNTs) have been identified as an efficient drug carrier. Here a controlled drug-delivery system based on SWNTs coated with doxorubicin (DOX) through hydrazone bonds was developed, because the hydrazone bond is more sensitive to tumor microenvironments than other covalent linkers. The SWNTs were firstly stabilized with polyethylene glycol (H2N-PEG-NH2). Hydrazinobenzoic acid (HBA) was then covalently attached on SWNTs via carbodiimide-activated coupling reaction to form hydrazine-modified SWNTs. The anticancer drug DOX was conjugated to the HBA segments of SWNT using hydrazine as the linker. The resulting hydrazone bonds formed between the DOX molecules and the HBA segments of SWNTs are acid cleavable, thereby providing a strong pH-responsive drug release, which may facilitate effective DOX release near the acidic tumor microenvironment and thus reduce its overall systemic toxicity. The DOX-loaded SWNTs were efficiently taken up by HepG2 tumor cells, and DOX was released intracellularly, as revealed by MTT assay and confocal microscope observations. Compared with SWNT-DOX conjugate formed by supramolecular interaction, the SWNT-HBA-DOX featured high weight loading and prolonged release of DOX, and thus improved its cytotoxicity against cancer cells. This study suggests that while SWNTs have great potential as a drug carrier, the efficient formulation strategy requires further study.

Keywords: carbon nanotubes, drug delivery, controlled release, SWNTs

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