Reduction-responsive worm-like nanoparticles for synergistic cancer chemo-photodynamic therapy.

Chemo-photodynamic therapy shows great potential for cancer treatment. However, the rational integration of chemotherapeutic agents and photosensitizers to construct an intelligent nanoplatform with synergistic therapeutic effect is still a great challenge. In this work, curcumin-loaded reduction-responsive prodrug nanoparticles of new indocyanine green (Cur@IR820-ss-PEG) were developed for synergistic cancer chemo-photodynamic therapy. Cur@IR820-ss-PEG exhibit high drug loading content and special worm-like morphology, contributing to their efficient cellular uptake. Due to the presence of the disulfide bond between IR820 and PEG, Cur@IR820-ss-PEG display reduction responsive drug release behaviors. The efficient cellular uptake and reduction triggered drug release of Cur@IR820-ss-PEG lead to their enhanced in vitro cytotoxicity against 4T1cells as compared to the mixture of IR820 and curcumin (IR820/Cur) under laser irradiation. Besides, Cur@IR820-ss-PEG exhibit prolonged blood half-life time, better tumor accumulation and retention, enhanced tumor hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial cell growth factor (VEGF) suppression effect as compared to IR820/Cur. In vivo antitumor activity study, Cur@IR820-ss-PEG effectively inhibit the tumor angiogenesis, which potentiates the PDT efficacy and leads to the best in vivo antitumor effect of Cur@IR820-ss-PEG. This work provides a novel and relatively simple strategy for synergistic cancer chemo-photodynamic therapy.

Potentiating photodynamic therapy of ICG-loaded nanoparticles by depleting GSH with PEITC.

Photodynamic therapy (PDT) is a clinically approved cancer treatment which utilizes reactive oxygen species (ROS) to eradicate cancer cells. But the high concentration of GSH inside tumor cells can neutralize the generated ROS during PDT, resulting in an insufficient therapeutic effect. To address this issue, we combined ICG-loaded nanoparticles with PEITC for potent PDT. ICG encapsulated in novel hydroxyethyl starch-oleic acid conjugate (HES-OA) nanoparticles (∼50 nm) exhibited excellent stability and efficient singlet oxygen generation under laser irradiation, promoted cellular uptake, and enhanced tumor accumulation, whilst PEITC depleted intracellular GSH significantly. As a result, PDT based on ICG-loaded NPs combined with PEITC synergistically suppressed cancer cells both in vitro and in vivo. Potentiating ICG-loaded NPs with PEITC represents a novel and efficient strategy to enhance PDT efficacy.

Nanocolloidosomes with Selective Drug Release for Active Tumor-Targeted Imaging-Guided Photothermal/Chemo Combination Therapy.

Selective drug release is highly desirable for photothermal/chemo combination therapy when two or even more theranostic agents are encapsulated together within the same nanocarrier. A conventional nanocarrier can hardly achieve this goal. Herein, doxorubicin and indocyanine green (DOX/ICG)-loaded nanocolloidosomes (NCs), with selective drug release, were fabricated as a novel multifunctional theranostic nanoplatform for photothermal/chemo combination therapy. Templating from galactose-functionalized hydroxyethyl starch-polycaprolactone (Gal-HES-PCL) nanoparticles-stabilized Pickering emulsions, the resultant DOX/ICG@Gal-HES-PCL NCs had a diameter of around 140 nm and showed an outstanding tumor-targeting ability, preferable tumor penetration capability, and promotion of photothermal effect. Moreover, these NCs can be used for NIR fluorescence imaging and thus render real-time imaging of solid tumors with high contrast. Collectively, such NCs achieved the best in vivo antitumor efficacy combined with laser irradiation compared with DOX/ICG@HES-PCL NCs and DOX/ICG mixture. These NCs are valuable for active tumor-targeted imaging-guided combination therapy against liver cancer and potentially other diseases.