Tuning the physicochemical properties of reticular covalent organic frameworks (COFs) for biomedical applications.

Since the first report by Yaghi's group in 2005, research enthusiasm has been increasingly raised to synthesize diverse crystalline porous materials as -B-O-, -C-N-, -C-C-, and -C-O- linkage-based COFs. Recently, the biomedical applications of COFs have become more and more attractive in biomedical applications, including drug delivery, bioimaging, biosensing, antimicrobial, and therapeutic applications, as these materials bear well-defined crystalline porous structures and well-customized functionalities. However, the clinical translation of these research findings is challenging due to the formidable hindrances for in vivo use, such as low biocompatibility, poor selectivity, and long bio-persistence. Some attempts have raised a promising solution towards these obstacles by tailored engineering the functionalities of COFs. To speed up the clinical translations of COFs, a short review of principles and strategies to tune the physicochemical properties of COFs is timely and necessary. In this review, we summarized the biomedical utilities of COFs and discussed the related key physicochemical properties. To improve the performances of COFs in biomedical uses, we propose approaches for the tailored functionalization of COFs, including large-scale manufacture, standardization in nanomedicines, enhancing targeting efficacy, maintaining predesigned functions upon transformations, and manipulation of multifunctional COFs. We expect that this minireview strengthens the fundamental understandings of property-bioactivity relationships of COFs and provides insights for the rational design of their high-order reticular structures.