Near-infrared light remote-controlled intracellular anti-cancer drug delivery using thermo/pH sensitive nanovehicle

Abstract

Stimuli-responsive drug delivery systems have been developed to enhance the tumor-targeting drug transportation and minimize the severe side effects along with the chemotherapy. In this study, a near-infrared (NIR) light triggered drug delivery system was developed based on the amphiphilic chitosan derivative-coated single-wall carbon nanotubes (CNT) encapsulated in the thermo/pH sensitive nanogel (CS/PNIPAAm@CNT). The PEG diacrylate (Mw=250Da) was applied in the present work to tune the nanoparticles with the phase transition temperature at ∼38°C, which was an attempt to match the prerequisite for the in vivo applications. Owing to the π–π stacking, hydrophobic interaction and the opportunity of Schiff-base formation between chitosan and doxorubicin (DOX), the nanoparticles possessed a relative high drug loading capacity (∼43%). The DOX loaded CS/PNIPAAm@CNT released DOX faster at 40°C than at 25°C, meanwhile faster at pH 5.0 in comparison with that at pH 7.4. Moreover, the rapid and repetitive release of DOX was observed when the DOX-loaded CS/PNIPAAm@CNT was irradiated under NIR light. Furthermore, DOX-loaded CS/PNIPAAm@CNT upon NIR irradiation showed significantly greater cytotoxicity in HeLa cells owing to NIR-triggered increase in temperature and enhanced DOX release. Confocal laser scanning microscopy (CLSM) was utilized to demonstrate the enhanced cell uptake of the as prepared nanoparticles and the faster drug release under the NIR irradiation and lower pH. All the results suggest that multifunctional DOX-loaded CS/PNIPAAm@CNT nanocomposite is a promising therapeutic nanocarrier for intracellular drug delivery with great potential for targeted cancer therapy.