A Porous Organic Framework‐Based Nanoplatform for Directional Destruction on Endoplasmic Reticulum to Enhance Tumor Immunotherapy

Abstract With the development of oncology, immunotherapy holds great promise for tumor treatment. However, immunogenic cell death (ICD), an important stimulator of immune response, often fails to trigger effective immunotherapy. Herein, a strategy to cause endoplasmic reticulum (ER) stress for further amplifying ICD is reported. A porous organic framework‐based nanoplatform (PLGH‐T ER ) with good targeting ER ability for chemiluminescence resonance energy transfer (CRET) based‐photodynamic therapy (PDT) is developed, which solves the limitations of the restricted penetration of light and suboptimal bioavailability of commonly used photosensitizers (PS). Once accumulated in ER, PLGH‐T ER activates the translation from glucose to H 2 O 2 for starvation therapy and further elicit CRET‐based‐PDT, which results in ER stress and amplified ICD ultimately. Then, the amplified ICD promotes the release of damage‐associated molecular patterns , realizing enhanced immunotherapy. Consequently, PLGH‐T ER can achieve directional destruction on ER and inhibit tumor invasion and recurrence, which expands the application of porous organic framework for tumor immunotherapy.