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 (1O2)‐stored covalent organic framework (COF) nanoparticles loading the near‐infrared (NIR) dye cypate, which realize oxygen‐independent 1O2 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 1O2‐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, 1O2 is produced by the photosensitizer motifs and is successfully stored by the 1O2‐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 1O2 to ablate tumors via O2‐independent concurrent PTT/PDT. Accordingly, the COF nanocarriers of 1O2 provide a paradigm to develop O2‐independent concurrent PTT/PDT for precise cancer treatment upon NIR irradiation.

Pore-engineered nanoarchitectonics for cancer therapy

“…Boronbased COFs have been widely explored as nanocarriers for various drugs; however, they suffer from hydrolytic degradation by water 79 . Hence, new types of linkages, such as hydrazone linkages, Schiff-base-type imine linkages, and covalent triazine-based frameworks, have been developed for COF-based nanocarriers [80][81][82][83] . For instance, Bhunia et al synthesized a perylene-based COF, which acts as a reservoir for mitotoxantrone drugs.…”

Insights into the organic semiconducting photosensitizers for hypoxia-tolerant type I photodynamic therapy

“…Covalent organic frameworks (COFs) are a new class of porous organic semiconducting polymers with covalently linked organic molecules, which are suitable for biomedical applications, including drug delivery, deep-tissue imaging, and phototherapy applications, such as PDT and photothermal therapy (PTT), owing to the high structural stability, thermal stability, large surface area, high crystallinity, and tunable functionalities [4,30,[76][77][78].…”

Salt-Assisted Fabrication of a Water-Based Covalent Organic Framework Ink and Its Hybrid Films for Photothermal Actuators

“…Two-dimensional covalent organic frameworks (2D-COFs) are a class of crystalline porous materials that consist of lightweight elements (H, B, C, Si, N, O) linked by strong covalent bonds via dynamic covalent chemistry, which is different from traditional organic polymer materials. − The reversible formation and breaking of covalent bonds allows the self-repair of internal defects, resulting in a long-range ordered porous structure. − Moreover, the highly ordered and low-density framework of COFs provides an opportunity to incorporate large π-conjugated structures and π–π multilayer stack at a molecular level, making them attractive materials for energy conversion and storage, especially photothermal conversion. − Despite their potential, COFs have not been extensively explored for soft photothermal actuators due to anisotropy growth, which leads to difficulties in film formation …”