Engineering hydrogen-bonded organic frameworks for efficient enzyme encapsulation and diagnostic applications

Abstract

Hydrogen-bonded organic frameworks (HOFs) have garnered considerable attention as versatile, metal-free porous materials with exceptional potential for enzyme encapsulation and biosensing applications. Despite their inherent biocompatibility and tunable porosity, challenges such as stability under physiological conditions and scalable synthesis remain. In this review, we present a comprehensive overview of recent advances in HOF engineering to enhance enzyme encapsulation efficiency, stabilization, and catalytic activity. This framework integrates molecular design strategies including hydrogen bonding, selective biomolecule recognition, pore size tuning, and co-encapsulation with cofactors to create a protective microenvironment that prolongs enzymatic function under harsh conditions. Cutting-edge HOF-based materials are also highlighted as high-performance platforms for biosensing, integrating optical, electrochemical, and Raman-based methods to achieve ultrasensitive biomolecule and disease marker detection. Furthermore, we discuss the emerging biomedical and therapeutic applications of HOF-based composites, including cell protection, targeted drug delivery, and bioorthogonal catalysis. Key challenges, such as framework stability under physiological conditions, scalability of synthesis, and device integration, are critically evaluated, along with future research directions for clinical translation and industrial application. Collectively, these advances position HOF-based systems as next-generation materials for robust, efficient, and multifunctional biocatalysis and diagnostics.

Keywords:Diagnostic applications, Drug delivery, Enzyme encapsulation, Hydrogen-bonded organic frameworks (HOFs), Molecular recognition.