Covalent organic frameworks as emerging host platforms for enzyme immobilization and robust biocatalysis - A review.

Finding a personalized nano theranostics solution, a nanomedicine for cancer diagnosis and therapy, is among the top challenges of current medicinal science. Porous organic polymers (POPs) are permanent porous organic materials prepared by linking relatively rigid multidimensional organic building blocks. POP nanoparticles have a remarkable advantage for cancer theranostics owing to their specific physicochemical characteristics such as high surface area, convincing pore size engineering, stimuli-responsive degradability, negligible toxicity, open covalent post-synthesis modification possibilities etc. POPs have crystalline and non-crystalline characteristics; crystalline POPs are popularly known as covalent organic frameworks (COFs), and have shown potential application across research areas in science. The early research and development on theranostics applications of nanoscale POPs has shown tremendous future potential for clinical translation. This tutorial review highlights the recently developed promising applications of nPOPs in drug loading, targeted delivery, endogenous and exogenous stimuli-responsive release, cancer imaging and combination therapy, regardless of their crystalline and poorly crystalline properties. The review will provide a platform for the future development and clinical translation of nPOPs by solving fundamental challenges of cancer nanomedicines in drug loading efficiency, size-optimization, biocompatibility, dispersibility and cell uptake ability.

Nanoscale porous organic polymers for drug delivery and advanced cancer theranostics.

Chemodynamic therapy (CDT), which induces cell death by decomposing high levels of H2 O2 in tumor cells into highly toxic ·OH, is recognized as a promising antineoplastic approach. However, current CDT approaches are often restricted by the highly controlled and upregulated cellular antioxidant defense. To enhance ·OH-induced cellular damage by CDT, a covalent organic framework (COF)-based, ferrocene (Fc)- and glutathione peroxidase 4 (GPX4) inhibitor-loaded nanodrug, RSL3@COF-Fc (2b), is fabricated. The obtained 2b not only promotes in situ Fenton-like reactions to trigger ·OH production in cells, but also attenuates the repair mechanisms under oxidative stress via irreversible covalent GPX4 inhibition. As a result, these two approaches synergistically result in massive lipid peroxide accumulation, subsequent cell damage, and ultimately ferroptosis, while not being limited by intracellular glutathione. It is believed that this research provides a paradigm for enhancing reactive oxygen species-mediated oncotherapy through redox dyshomeostasis and may provide new insights for developing COF-based nanomedicine.

A Ferrocene-Functionalized Covalent Organic Framework for Enhancing Chemodynamic Therapy via Redox Dyshomeostasis.

Porous organic polymers (POPs) have emerged as a new class of multifunctional porous materials and received tremendous research attention from both academia and industry. Most POPs are constructed from versatile organic small molecules with diverse linkages through strong covalent bonds. Owing to their high surface area and porosity, low density, high stability, tunable pores and skeletons, and ease of functionalization, POPs have been extensively studied for gas storage and separation, heterogeneous catalysis, biomedicine, sensing, optoelectronics, energy storage and conversion, etc. Particularly, POPs are excellent platforms with exciting opportunities for biomedical applications. Consequently, considerable efforts have been devoted to preparing POPs with an emphasis on their biomedical applications. In this review, first, we briefly describe the different subclasses of POPs and their synthetic strategies and functionalization approaches. Then, we highlight the state-of-the-art progress in POPs for a variety of biomedical applications such as drug delivery, biomacromolecule immobilization, photodynamic and photothermal therapy, biosensing, bioimaging, antibacterial, bioseparation, etc. Finally, we provide our thoughts on the fundamental challenges and future directions of this emerging field. 

Emerging porous organic polymers for biomedical applications

Covalent organic frameworks (COFs) are a class of organic crystalline porous materials discovered in the early 21st century that have become an attractive class of emerging materials due to their high crystallinity, intrinsic porosity, structural regularity, diverse functionality, design flexibility, and outstanding stability. However, many chemical and physical properties strongly depend on the presence of metal ions in materials for advanced applications, but metal-free COFs do not have these properties and are therefore excluded from such applications. Metalated COFs formed by combining COFs with metal ions, while retaining the advantages of COFs, have additional intriguing properties and applications, and have attracted considerable attention over the past decade. This review presents all aspects of metalated COFs, from synthetic strategies to various applications, in the hope of promoting the continued development of this young field.

Metalated covalent organic frameworks: from synthetic strategies to diverse applications.

Cancer nanomedicine is one of the most promising domains that has emerged in the continuing search for cancer diagnosis and treatment. The rapid development of nanomaterials and nanotechnology provide a vast array of materials for use in cancer nanomedicine. Among the various nanomaterials, covalent organic frameworks (COFs) are becoming an attractive class of upstarts owing to their high crystallinity, structural regularity, inherent porosity, extensive functionality, design flexibility, and good biocompatibility. In this comprehensive review, recent developments and key achievements of COFs are provided, including their structural design, synthesis methods, nanocrystallization, and functionalization strategies. Subsequently, a systematic overview of the potential oncotherapy applications achieved till date in the fast-growing field of COFs is provided with the aim to inspire further contributions and developments to this nascent but promising field. Finally, development opportunities, critical challenges, and some personal perspectives for COF-based cancer therapeutics are presented.

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Guang-Bo Wang

Papers

Nanoscale covalent organic frameworks as theranostic platforms for oncotherapy: synthesis, functionalization, and applications