A versatile diketopyrrolopyrrole-based photosensitizing nanoplatform with high photostability and photoactivity for metastatic breast cancer treatment

Owing to the merits of acceptable biocompatibility, excellent efficacy and minimal invasiveness, photodynamic therapy (PDT) represents a promising alternative approach for fighting against malignant tumor. However, the photobleaching, photodegradation and dark toxicity of traditional photosensitizers limit the therapeutic efficacy and clinical use of PDT. In present work, we synthesized a diketopyrrolopyrrole-based photosensitizer, AN(DPP)2, with excellent fluorescence emission, photodynamic performance and photostability. We then fabricated a versatile photosensitizing nanoplatform composed of AN(DPP)2-loaded PEGylated black phosphorous nanosheets (named AN/pBPN), for synergetic photodynamic-photothermal therapy (PDT/PTT) against metastatic breast cancer. AN/pBPN exhibited a multitude of notable superiorities in terms of superior optical characters, favorable photodynamic and photothermal performance in physiological environment, and excellent internalization efficiency toward tumor cells. Upon light irradiation, abundant singlet oxygen and hyperthermia were generated by AN/pBPN, resulting in a remarkable antitumor effect toward 4T1 cells. In vivo studies verified that AN/pBPN showed potent light-triggered suppression of tumor growth as well as distant pulmonary metastasis, accompanied by minimal safety concern in metastatic breast cancer mouse model. Collectively, multifunctional diketopyrrolopyrrole-based photosensitizing nanoplatform with prominent photoactivity, acceptable biosafety, powerful antitumor and anti-metastasis activity, such as AN/pBPN, might be a promising nanomedicine for combating malignant tumor via synergetic phototherapy.