Covalent Organic Frameworks: Opportunities for Rational Materials Design in Cancer Therapy.

Nanomedicines are extensively used in cancer therapy. Covalent organic frameworks (COFs) are crystalline organic porous materials with several benefits for cancer therapy, including porosity, design flexibility, functionalizability, and biocompatibility. This review examines the use of COFs in cancer therapy from the perspective of reticular chemistry and function-oriented materials design.

A Multifunctional Covalent Organic Framework Nanozyme for Promoting Ferroptotic Radiotherapy against Esophageal Cancer.

Radiotherapy is inevitably accompanied by some degree of radiation resistance, which leads to local recurrence and even therapeutic failure. To overcome this limitation, herein, we report the room-temperature synthesis of an iodine- and ferrocene-loaded covalent organic framework (COF) nanozyme, termed , for the enhancement of radiotherapeutic efficacy in the treatment of radioresistant esophageal cancer. The iodine atoms on the COF framework not only exerted a direct effect on radiotherapy, increasing its efficacy by increasing X-ray absorption, but also promoted the radiolysis of water, which increased the production of reactive oxygen species (ROS).

A reactive oxygen species-responsive covalent organic framework for tumor combination therapy.

Herein, we report the first reactive oxygen species (ROS)-responsive dithioketal-linked covalent organic framework (COF) for synergetic chemotherapy and photodynamic therapy (PDT) of cancer. The singlet oxygen (O)-responsive COF dissociation and DC_AC50 drug release complement and reinforce each other to allow an efficient combination of PDT and chemotherapy.

An iodide-containing covalent organic framework for enhanced radiotherapy.

Metal-free radiosensitizers, particularly iodine, have shown promise in enhancing radiotherapy due to their suitable X-ray absorption capacities and negligible biotoxicities. However, conventional iodine compounds have very short circulating half-lives and are not retained in tumors very well, which significantly limits their applications. Covalent organic frameworks (COFs) are highly biocompatible crystalline organic porous materials that are flourishing in nanomedicine but have not been developed for radiosensitization applications.

A biodegradable covalent organic framework for synergistic tumor therapy.

Stimulus-responsive biodegradable nanocarriers with tumor-selective targeted drug delivery are critical for cancer therapy. Herein, we report for the first time a redox-responsive disulfide-linked porphyrin covalent organic framework (COF) that can be nanocrystallized by glutathione (GSH)-triggered biodegradation. After loading 5-fluorouracil (5-Fu), the generated nanoscale COF-based multifunctional nanoagent can be further effectively dissociated by endogenous GSH in tumor cells, releasing 5-Fu efficiently to achieve selective chemotherapy on tumor cells.

Construction of Covalent Organic Frameworks via Multicomponent Reactions.

Multicomponent reactions (MCRs) combine at least three reactants to afford the desired product in a highly atom-economic way and are therefore viewed as efficient one-pot combinatorial synthesis tools allowing one to significantly boost molecular complexity and diversity. Nowadays, MCRs are no longer confined to organic synthesis and have found applications in materials chemistry. In particular, MCRs can be used to prepare covalent organic frameworks (COFs), which are crystalline porous materials assembled from organic monomers and exhibit a broad range of properties and applications.

A vinyl-decorated covalent organic framework for ferroptotic cancer therapy visible-light-triggered cysteine depletion.

Biothiols, including glutathione (GSH) and cysteine, are important reductants that maintain intracellular redox homeostasis. Recent studies have demonstrated that cysteine deprivation is a more effective antitumor strategy than GSH depletion. However, the lack of highly chemoselective and tumor-specific cysteine-consuming reagents limits the practical application of cysteine deprivation.

Ambient synthesis of an iminium-linked covalent organic framework for synergetic RNA interference and metabolic therapy of fibrosarcoma.

Small interfering RNA (siRNA)-mediated gene silencing is a promising therapeutic approach. Herein, we report the ambient synthesis of a positively charged iminium-linked covalent organic framework by a three-component one-pot reaction. Through anion exchange and siRNA adsorption, the resulting multifunctional siRNA@ABMBP-COF, which possesses both the HK2 inhibitor 3-bromopyruvate and SLC7A11 siRNA, exhibits powerful synergistic antitumor activity against fibrosarcoma the ferroptosis and apoptosis pathways.

Metalated covalent organic frameworks: from synthetic strategies to diverse 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.

[Heat shock protein 90 in male reproduction].

Heat shock protein 90 (Hsp90), as a member of the Hsp family and widely found in the gonads of humans and animals, plays an essential role in male reproduction and induces various changes in the process of reproduction. Hsp90 regulates the division of germ cells and participates in spermatogenesis, location of germ cells, formation of sperm microtubes, protection of sperm from oxidative stress, and inducement of acrosomal reaction. Studies showed significant changes in location and expression of Hsp90 in the sperm of oligospermia and asthenospermia patients.

Glutathione S-transferase kappa 1 is positively related with sperm quality of porcine sperm.

The glutathione S-transferase (GST) superfamily members play an important role in the male reproductive tract and sperm physiology. However, the expression profiles of some members of this protein family and their effect on sperm quality remain unclear. In this study, we found that GST kappa 1 (GSTK1) encoded protein is abundant in the testes and capacitated sperm acrosome.

Ferroptosis in cancer therapeutics: a materials chemistry perspective.

Ferroptosis, distinct from apoptosis, is a regulated form of cell death caused by lipid peroxidation that has attracted extensive research interest since it was first defined in 2012. Over the past five years, an increasing number of studies have revealed the close relationship between ferroptosis and materials chemistry, in particular nanobiotechnology, and have concluded that nanotechnology-triggered ferroptosis is an efficient and promising antitumor strategy that provides an alternative therapeutic approach, especially for apoptosis-resistant tumors. In this review, we summarize recent advances in ferroptosis-induced tumor therapy at the intersection of materials chemistry, redox biology, and tumor biology.

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

Chemodynamic therapy (CDT), which induces cell death by decomposing high levels of H O 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.

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

A Glycosylated Covalent Organic Framework Equipped with BODIPY and CaCO for Synergistic Tumor Therapy.

Ca , a ubiquitous but nuanced modulator of cellular physiology, is meticulously controlled intracellularly. However, intracellular Ca regulation, such as mitochondrial Ca buffering capacity, can be disrupted by O . Thus, the intracellular Ca overload, which is recognized as one of the important cell pro-death factors, can be logically achieved by the synergism of O with exogenous Ca delivery.

A carbon nanomaterial derived from a nanoscale covalent organic framework for photothermal therapy in the NIR-II biowindow.

Herein, we report a microporous carbon nanomaterial that was generated from a nanoscale covalent organic framework precursor via a simple pyrolysis approach. The obtained carbon-based nanoparticles possessed a broad NIR absorption capacity and exhibited a high level of photothermal conversion ability (η = 50.6%) in the NIR-II biowindow.

Covalent Organic Frameworks (COFs) for Cancer Therapeutics.

As newly emerged crystalline porous materials, covalent organic frameworks (COFs) possess fascinating structures and some specific features such as modularity, crystallinity, porosity, stability, versatility, and biocompatibility. Besides adsorption/separation, sensing, catalysis, and energy applications, COFs have recently shown a promise in biomedical applications. This contribution provides an overview of the recent developments of COF-based medicines in cancer therapeutics, including drug delivery, photodynamic therapy (PDT), photothermal therapy (PTT), and combined therapy.

Nanoscale Covalent Organic Framework for Combinatorial Antitumor Photodynamic and Photothermal Therapy.

Despite the excellent photodynamic and photothermal properties of organic molecular photosensitizers (PSs) and photothermal agents (PTAs), such as porphyrin and naphthalocyanine, their poor water solubility severely impedes their biological applications. Covalent organic frameworks (COFs), as an emerging class of organic crystalline porous materials, possess free active end groups (bonding defects) and large inner pores, which make them an ideal type of nanocarriers for loading hydrophobic organic molecular PSs and PTAs by both bonding defect functionalization (BDF) and guest encapsulation approaches to obtain multifunctional nanomedicines for PDT/PTT combination therapy. In this work, we report a nanoscale COF (NCOF) prepared a facile synthetic approach under ambient conditions.

A nanoscale metal-organic framework for combined photodynamic and starvation therapy in treating breast tumors.

We demonstrate herein an effective cascade reaction for combined photodynamic and starvation therapy in treating breast tumors based on a photosensitizer and CO prodrug decorated NMOF. The PDT-induced ROS can further trigger CO release, and the high antitumor efficiency derived from both 1O2 and CO is well confirmed by in vitro assays and in vivo trials.

Diiodo-Bodipy-Encapsulated Nanoscale Metal-Organic Framework for pH-Driven Selective and Mitochondria Targeted Photodynamic Therapy.

We report herein a new ZIF-90-based PDT agent which was synthesized by in situ assembly of imidazole-2-carboxaldehyde (IcaH), Zn(NO), and heavy atom iodine-attached Bodipy. The obtained 2I-BodipyPhNO@ZIF-90 (1) host-guest photosensitive system featured low cytotoxicity, good biocompatibility, pH-driven selective cancer cell uptake and release, mitochondria targeting, and highly efficient pH-triggered O generation. Therefore, it can be used as a high-performing PDT agent to selectively kill tumor cells.

One-Pot Synthetic Approach toward Porphyrinatozinc and Heavy-Atom Involved Zr-NMOF and Its Application in Photodynamic Therapy.

Herein, we report an iodine-attached Zn(II)-porphyrinic dicarboxylic building block (ZnDTPP-I-2H, 1) that can be introduced into UiO-66 NMOF via one-pot synthetic approach to generate a new ZnDTPP-I doped UiO-66 type nano metal-organic framework (NMOF) of ZnDTPP-I⊂UiO-66 (2). Compared to its homologous iodine-free NMOF of ZnDTPP⊂UiO-66 (4), ZnDTPP-I⊂UiO-66 (2) with heavy iodine atoms is a more effective nanosized photosensitizer for singlet oxygen generation under physiological conditions. As expected, 2 displayed a high photodynamic therapy efficacy for treatment of liver cancer cells in vitro.