Covalent Organic Framework Nanocarriers of Singlet Oxygen for Oxygen‐Independent Concurrent Photothermal/Photodynamic Therapy to Ablate Hypoxic Tumors

Abstract Photodynamic therapy (PDT) of cancers is seriously restricted by tumor hypoxia. In addition to the intrinsic hypoxic microenvironment, continuous photoirradiation further aggravates intratumoral hypoxia, thereby reducing the PDT effect significantly. Oxygen‐independent PDT is recognized as an efficient approach to overcome this issue. Herein, singlet oxygen ( 1 O 2 )‐stored covalent organic framework (COF) nanoparticles loading the near‐infrared (NIR) dye cypate, which realize oxygen‐independent 1 O 2 production for concurrent photothermal therapy (PTT) and PDT under NIR irradiation, are presented. The cypate‐loading COF nanoparticles are prepared by using the photosensitizers and 1 O 2 ‐stored molecules via formation of Schiff base bonds, followed by coverage of poly(vinyl pyrrolidone). The COF nanoparticles significantly improve the photostability and photothermal conversion efficiency of cypate by protecting them from photodegradation under NIR irradiation. Upon 660 nm laser irradiation, 1 O 2 is produced by the photosensitizer motifs and is successfully stored by the 1 O 2 ‐stored moieties. After intravenous injection and tumor accumulation, the COF nanoparticles can generate heat quickly upon 808 nm irradiation which induces the efficient release of the stored 1 O 2 to ablate tumors via O 2 ‐independent concurrent PTT/PDT. Accordingly, the COF nanocarriers of 1 O 2 provide a paradigm to develop O 2 ‐independent concurrent PTT/PDT for precise cancer treatment upon NIR irradiation.