A new NIR-triggered doxorubicin and photosensitizer indocyanine green co-delivery system for enhanced multidrug resistant cancer treatment through simultaneous chemo/photothermal/photodynamic therapy

It is a great challenge to combat multidrug resistant (MDR) cancer effectively. To address this issue, we developed a new near-infrared (NIR) triggered chemotherapeutic agent doxorubicin (DOX) and photosensitizer indocyanine green (ICG) co-release system by aid of NIR induced photothermal effect of gold nanocages (AuNCs) and temperature sensitive phase-change property of 1-tetradecanol at its melting point of 39 °C, which could simultaneously exerted chemo/photothermal/photodynamic treatment on MDR human breast cancer MCF-7/ADR cells. This nano-sized system was constructed by filling the interior of AuNCs with DOX, ICG and 1-tetradecanol, and modifying the surface with biotinylated poly (ethylene glycol) via Au-S bonds, termed as DOX/ICG@biotin-PEG-AuNC-PCM. The DOX and ICG co-release from DOX/ICG@biotin-PEG-AuNC-PCM was much faster in PBS at 40 °C or under 808 nm NIR irradiation at 2.5 W/cm2 than at 37 °C (e.g. 67.27% or 80.31% vs. 5.57% of DOX, 76.08% vs. 3.83% of ICG for 20 min). The flow cytometry and confocal laser scanning microscopy (CLSM) results showed, the AuNCs were taken up by MCF-7/ADR cells via endocytosis, thus enhancing DOX uptake; the biotin on AuNCs facilitated this endocytosis; NIR irradiation caused the heating of the AuNCs, triggering the DOX and ICG co-release and enhancing the distribution of DOX in nuclei, the released ICG generated ROS to take photodynamic therapy. Due to the above unique properties, DOX/ICG@biotin-PEG-AuNC-PCM exerted excellent anti-tumor effects under NIR irradiation, its IC50 against MCF-7/ADR cells was very low, only 0.48 µg/mL, much smaller than that of free DOX (74.51 μg/mL).Statement of SignificanceA new near-infrared (NIR) triggered chemotherapeutic agent doxorubicin (DOX) and photosensitizer indocyanine green (ICG) co-release system by aid of NIR induced photothermal effect of gold nanocages (AuNCs) and temperature sensitive phase-change property of 1-tetradecanol at its melting point of 39 °C, was prepared, termed as DOX/ICG@biotin-PEG-AuNC-PCM, which could simultaneously exerted chemo/photothermal/photodynamic treatment on MDR human breast cancer MCF-7/ADR cells. DOX/ICG@biotin-PEG-AuNC-PCM exerted excellent anti-tumor effects under NIR irradiation, its IC50 against MCF-7/ADR cells was very low, only 0.48 µg/mL, much smaller than that of free DOX (74.51 μg/mL).

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