Accelerated killing of cancer cells using a multifunctional single-walled carbon nanotube-based system for targeted drug delivery in combination with photothermal therapy

• Published in: International journal of nanomedicine 2013-01, Vol.8 (1), p.2653-2667, Article 2653
• Main Authors: Jeyamohan, Prashanti, Hasumura, Takashi, Nagaoka, Yutaka, Yoshida, Yasuhiko, Maekawa, Toru, Kumar, D Sakthi
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Breast cancer; cancer; Cancer cells; Cancer therapies; Cell Line; Cell Survival - drug effects; Cell Survival - radiation effects; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacokinetics; Doxorubicin - pharmacology; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug Carriers - pharmacology; Drug delivery systems; Drugs; Health aspects; Humans; Lasers; Materials Testing; MCF-7 Cells; Mice; nanotherapy; Nanotubes; Nanotubes, Carbon - chemistry; Optical properties; Original Research; Phototherapy - methods; photothermal therapy; Physiological aspects; Spectroscopy, Near-Infrared; SWCNTs; targeted drug delivery; Vehicles
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/ijn.s46054

The photothermal effect of single-walled carbon nanotubes (SWCNTs) in combination with the anticancer drug doxorubicin (DOX) for targeting and accelerated destruction of breast cancer cells is demonstrated in this paper. A targeted drug-delivery system was developed for selective killing of breast cancer cells with polyethylene glycol biofunctionalized and DOX-loaded SWCNTs conjugated with folic acid. In our work, in vitro drug-release studies showed that the drug (DOX) binds at physiological pH (pH 7.4) and is released only at a lower pH, ie, lysosomal pH (pH 4.0), which is the characteristic pH of the tumor environment. A sustained release of DOX from the SWCNTs was observed for a period of 3 days. SWCNTs have strong optical absorbance in the near-infrared (NIR) region. In this special spectral window, biological systems are highly transparent. Our study reports that under laser irradiation at 800 nm, SWCNTs exhibited strong light-heat transfer characteristics. These optical properties of SWCNTs open the way for selective photothermal ablation in cancer therapy. It was also observed that internalization and uptake of folate-conjugated NTs into cancer cells was achieved by a receptor-mediated endocytosis mechanism. Results of the in vitro experiments show that laser was effective in destroying the cancer cells, while sparing the normal cells. When the above laser effect was combined with DOX-conjugated SWCNTs, we found enhanced and accelerated killing of breast cancer cells. Thus, this nanodrug-delivery system, consisting of laser, drug, and SWCNTs, looks to be a promising selective modality with high treatment efficacy and low side effects for cancer therapy.