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Porphyrins coordinated with platinum­(II) chemotherapeutic drugs are attractive for the development of photosensitizers for photodynamic therapy (PDT) of cancer. In this paper, inorganic and metal–organic nanocomposites were synthesized with cascade-responsive imaging and photochemical synergistic effects. After endo/lysosomal escape, the outer metal–organic frameworks were degraded, leading to the release of an excellent photosensitizer (tetrapyridylporphyrin, PtTPyP). Subsequently, doxorubicin (DOX), inserted in the adenosine triphosphate (ATP) aptamer-functionalized gold nanoparticles, was released under the stimulation of endogenous ATP, synergistically enhancing cancer treatment. Fluorescence imaging allowed tracking of PtTPyP and DOX for real-time detection and on-demand therapy. This strategy endowed the nanocomposites with stability, responsiveness, effectiveness, and ease of synthesis, namely, sTREE strategy. Accordingly, our demonstration provided a promising and smart nanocarrier for imaging and drug delivery.

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