The combination of photodynamic therapy (PDT) and chemotherapy (CT) offers a promising approach for the tumor eradication for overcoming multidrug resistance (MDR), which is a major obstacle to effective cancer treatment. However, for PDT, simultaneously achieving near-infrared (NIR) emission and efficient reactive oxygen species (ROS) generation with low dark toxicity is urgently needed but remains challenging. Herein, a series of novel fluorophores with strong NIR emission, hybridized local and charge transfer characteristics, good two-photon absorption, high photostability, low dark cytotoxicity and excellent ROS generation ability are developed. By encapsulating the NIR fluorophore (DEB-BDTO) as a photosensitizer along with a drug resistance inhibitor tariquidar (TQR) within a polymeric prodrug (PMP), a reduction-sensitive drug co-delivery system (DEB/TQR@PMP micelles) is constructed. The DEB/TQR@PMP micelles exhibit a prominent synergistic lethal effect of PDT and CT on SKOV-3 cells and SKOV-3/MDR cells, and can apparently enhance the inhibition of tumor growth compared with sole PDT or CT in the tumor-bearing mouse model. Both in vitro and in vivo experiments prove that the new NIR fluorophores are excellent photosensitizers and can furnish an efficient combination therapy of image-guided PDT and CT within drug delivery micelles, which is particularly useful for eradicating multidrug resistance cancer.
Keywords: Chemotherapy; Drug delivery; Near-infrared fluorophore; Photodynamic therapy; Photosensitizer.
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