Covalent organic framework nanoparticles: Overcoming the challenges of hypoxia in cancer therapy

Hypoxia, or low oxygen levels, is a common feature of the tumor microenvironment. It is caused by the aggressive proliferation of cancer cells, which consume more oxygen than healthy cells. Hypoxia not only activates several signaling pathways that promote tumor growth, and metastasis but also increases resistance to conventional cancer treatments. The introduction of covalent organic frameworks (COFs), with their porous structure, high stability, tunable properties, large surface area, and unrivaled biocompatibility, has offered promising prospects for resolving hypoxia-specific challenges. This write-up critically explores the COFs in enhancing oxygen delivery, reactive oxygen species (ROS) generation, optimized drug delivery, and enabling hypoxia-specific imaging. Furthermore, it outlines how COFs facilitate various hypoxia-targeting therapeutic modalities such as chemotherapy, type-I and type-II photodynamic therapy, photothermal therapy, sonodynamic therapy, and immunotherapy. By evaluating the latest research findings and their implications, this review offers insights into the potent role of COFs in curtailing hypoxia and bolstering cancer treatment efficiency. The overarching goal of this assessment is to enrich our understanding of hypoxia-specific cancer therapy strategies, crediting the pivotal role of COFs. It is hoped that this greater comprehension of the abilities and constraints of COFs will pave the way to conceive more potent and targeted therapeutic interventions, thereby enhancing patient outcomes in the complex terrain of cancer therapeutics.