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Pharm Res (2013) 30:27572771 DOI 10.1007/s11095-013-1095-3
RESEARCH PAPER
NIR-/pH-Responsive Drug Delivery of Functionalized Single-Walled Carbon Nanotubes for Potential Application in Cancer Chemo-Photothermal Therapy
Lei Wang & Jinjin Shi & Xin Jia & Ruiyuan Liu & Honghong Wang & Zhenzhen Wang & Lulu Li & Jing Zhang & Chaofeng Zhang &
Zhenzhong Zhang
Received: 16 January 2013 /Accepted: 28 May 2013 /Published online: 14 June 2013 # Springer Science+Business Media New York 2013
ABSTRACTPurpose To establish a NIR (near infrared)-/pH-responsive and sustained-release tumor-targeting drug delivery system (SWNTPEI/DOX/NGR).
Methods Functionalized SWNTs with polymerised polymeric poly(ethylene imine) was linked NGR (Asn-Gly-Arg) tumor-targeting peptide by DSPE-PEG2000-Maleimide via the maleimide group and sulfhydryl group of cysteine, in the end, doxorubicin (DOX) was attached to SWNT-PEI to obtain a SWNTPEI/DOX/NGR delivery system.
Results The SWNT-PEI/DOX/NGR delivery system has significantly sustained-release effect and the slow release of DOX in normal tissues contribute to reduced systemic toxicity, while under 808 nm NIR laser irradiation or under lower pH environment the release of DOX can be accelerated.
Conclusions Due to hyperthermia sensitizer effect of DOX, chemo-photothermal exemplified by SWNT-PEI/DOX/NGR tumor-targeting delivery system is a promising approach to anticancer therapy in vivo or in vitro.
KEY WORDS near infrared-responsive . pH-responsive . single-walled carbon nanotubes . sustained-release . tumor-targeting
ABBREVIATIONSDOX doxorubicinDPM DSPE-PEG2000-Maleimide NIR near infraredSWNT-PEI polyethylenimine functionalized single-walled carbon nanotubes SWNTs single-walled carbon nanotubes
INTRODUCTION
In recent years, intelligent drug delivery systems have attracted considerable attention due to their response to external stimuli, such as temperature, pH, electric/magnetic field, light and near infrared (NIR) laser irradiation (14). Compared with traditional drug carriers, the intelligent drug delivery system could carry drug more effectively to the targeted tissue of complicated diseases such as cancers.
NIR-/pH-stimuli responsive carriers have been reported broadly. These two factors NIR and pH could be regulated easily by external triggers (57). Therefore, these NIR-responsive carriers were used in tumor local photothermal therapy due to the increasing selectivity of drugs towards tumor cells. It is known that tumor tissues have lower pH value than normal tissues (8), and doxorubicin (DOX) could be liberated rapidly in the acidic microenvironment in vitro and in vivo (9,10).
It has been proved that long-term exposure of ailing tissues to moderate drug concentrations using controlled or sustained release formulations...