A light-induced nitric oxide controllable releasenano-platform based on diketopyrrolopyrrolederivatives for pH-responsive photodynamic/photothermal synergistic cancer therapy

摘要

Emerging treatment approaches, such as gas therapy (GT), photodynamic therapy (PDT) and photothermaltherapy (PTT), have received widespread attention. The development of an intelligent multifunctional nanoplatform responding to tumor microenvironments for multimodal therapy is highly desirable. Herein,a near-infrared (NIR) light-responsive nitric oxide (NO) photodonor (4-nitro-3-trifluoromethylaniline, NF)and a pH-sensitive group (dimethylaminophenyl) have been introduced into a diketopyrrolopyrrole core(denoted as DPP-NF). The DPP-NF nanoparticles (NPs) can be activated under weakly acidic conditionsof lysosomes (pH 4.5–5.0) to generate reactive oxygen species (ROS) and enhance photothermalefficiency. The fluorescence detection demonstrated that NO controllable release can be realized by“on–off” switching of the NF unit under NIR light irradiation or dark conditions. The controllable NOrelease of DPP-NF NPs can not only trigger tumor cell death by DNA damage, but also overcome PDTinefficiencies caused by hypoxia in tumors. Additionally, DPP-NF NPs displayed 45.6% photothermalconversion efficiency, making them superior to other reported DPP derivatives. In vitro studies showedthat DPP-NF NPs possessed low dark toxicity and high phototoxicity with a half-maximal inhibitoryconcentration of about 38 mg mL1. In vivo phototherapy indicated that DPP-NF NPs exhibited excellenttumor phototherapeutic efficacy with passive targeting of the tumor site via the enhanced permeabilityand retention (EPR) effect. These results highlight that the nano-platform has promising potential forNO-mediated multimodal synergistic phototherapy in clinical settings.