Although combined chemotherapy (Chemo), photothermal (PTT) and photodynamic (PDT) in cancer therapy has drawn significant attention due to its superior anticancer ability, the required high intensity of irradiation results in serious photo-toxicity to healthy neighboring cells, and thus limits its biomedical applications. Herein, we developed an ultralow-intensity near infrared (NIR) light synchronously activated collaborative Chemo/PTT/PDT nanoplatform. The nanoplatform is composed of a highly emissive upconversion (UC) core, chlorin e6 (Ce6) photosensitizer and the anticancer drug doxorubicin hydrochloride (DOX) co-loaded in a mesoporous silica (MS) shell, and polyethylene glycol-modified graphene (PGO) acts as both the photothermal reagent and smart switch for promoted drug release. Upon 808 nm NIR light exposure with ultralow intensity (0.25 W cm-2), which is below the maximum permissible exposure (MPE, 0.33 W cm-2) for skin, the mild hyperpyrexia of PGO induced both cancer cell irreversible death for PTT and greatly promoted drug release for enhanced Chemo. On the other hand, the upconverted 660 nm light from UC activated Ce6 to generate reactive oxygen species for PDT, while the upconverted 540 nm light from UC could be employed for visualizing the treatment process. The in vitro and in vivo anticancer experiments demonstrate that the ultralow-intensity NIR light synchronously activated Chemo/PTT/PDT nanoplatform exhibits remarkable therapeutic efficacy with minimal photodamage.
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