Therapeutic Potency of NO Loaded into Anticancer Copper Metal-Organic Framework through Nonclassical Hydrogen Bonding.

Metal-organic frameworks (MOFs) are potential exogenous scaffolds for therapeutic nitric oxide (NO) delivery because they can store drug or bioactive gas molecules within pores or on active metal sites. Herein, we employed a Cu-MOF coordinated with glutarate (glu) and 1,2-bis(4-pyridyl)ethane (bpa) to obtain NO-loaded Cu-MOF (NO⊂Cu-MOF). NO loading transformed the space group of Cu-MOF from monoclinic C2/c to triclinic P-1 through nonclassical hydrogen bonding with glu and bpa. Cu-MOF showed good stability in deionized water and phosphate-buffered saline. NO⊂Cu-MOF released up to 1.10 µmol mg-1 NO over 14.6 h at 37 °C, which is suitable for therapeutic applications. NO⊂Cu-MOF showed moderate biocompatibility with L-929 cells and significant anticancer activity against HeLa cells, suggesting an apoptosis-mediated cell death mechanism. These insights into NO bonding modes with Cu-MOF that enable controlled NO release can inspire the design of functional MOFs as hybrid NO donors for drug delivery.

Controllable Nitric Oxide Storage and Release in Cu-BTC: Crystallographic Insights and Bioactivity.

Crystalline metal-organic frameworks (MOFs) are extensively used in areas such as gas storage and small-molecule drug delivery. Although Cu-BTC (1, MOF-199, BTC: benzene-1,3,5-tricarboxylate) has versatile applications, its NO storage and release characteristics are not amenable to therapeutic usage. In this work, micro-sized Cu-BTC was prepared solvothermally and then processed by ball-milling to prepare nano-sized Cu-BTC (2). The NO storage and release properties of the micro- and nano-sized Cu-BTC MOFs were morphology dependent. Control of the hydration degree and morphology of the NO delivery vehicle improved the NO release characteristics significantly. In particular, the nano-sized NO-loaded Cu-BTC (NO⊂nano-Cu-BTC, 4) released NO at 1.81 µmol·mg-1 in 1.2 h in PBS, which meets the requirements for clinical usage. The solid-state structural formula of NO⊂Cu-BTC was successfully determined to be [CuC6H2O5]·(NO)0.167 through single-crystal X-ray diffraction, suggesting no structural changes in Cu-BTC upon the intercalation of 0.167 equivalents of NO within the pores of Cu-BTC after NO loading. The structure of Cu-BTC was also stably maintained after NO release. NO⊂Cu-BTC exhibited significant antibacterial activity against six bacterial strains, including Gram-negative and positive bacteria. NO⊂Cu-BTC could be utilized as a hybrid NO donor to explore the synergistic effects of the known antibacterial properties of Cu-BTC.

Delivery of nitric oxide-releasing silica nanoparticles for in vivo revascularization and functional recovery after acute peripheral nerve crush injury.

Nitric oxide (NO) has been shown to promote revascularization and nerve regeneration after peripheral nerve injury. However, in vivo application of NO remains challenging due to the lack of stable carrier materials capable of storing large amounts of NO molecules and releasing them on a clinically meaningful time scale. Recently, a silica nanoparticle system capable of reversible NO storage and release at a controlled and sustained rate was introduced. In this study, NO-releasing silica nanoparticles (NO-SNs) were delivered to the peripheral nerves in rats after acute crush injury, mixed with natural hydrogel, to ensure the effective application of NO to the lesion. Microangiography using a polymer dye and immunohistochemical staining for the detection of CD34 (a marker for revascularization) results showed that NO-releasing silica nanoparticles increased revascularization at the crush site of the sciatic nerve. The sciatic functional index revealed that there was a significant improvement in sciatic nerve function in NO-treated animals. Histological and anatomical analyses showed that the number of myelinated axons in the crushed sciatic nerve and wet muscle weight excised from NO-treated rats were increased. Moreover, muscle function recovery was improved in rats treated with NO-SNs. Taken together, our results suggest that NO delivered to the injured sciatic nerve triggers enhanced revascularization at the lesion in the early phase after crushing injury, thereby promoting axonal regeneration and improving functional recovery.

Potential Protective Effect of Nitric Oxide-Releasing Nanofibers in Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury.

Nitric oxide (NO) is involved in several physiological processes including vasodilation, angiogenesis, immune response, and wound healing, as well as preventing ischemia/reperfusion injury in many organs such as the heart, liver, lungs, and kidneys. Recently, various NO delivery systems such as nanoparticles, nanorods, and nanofibers have been widely studied as potential therapeutic agents. In particular, NO-releasing nanofibers have been attracting much attention for various medicinal applications including regenerative medicine, wound dressings, and coatings for implantable medical devices, due to their flexible and open architectures. In this study, we prepared biocompatible NO-releasing nanofibers by electrospinning using mixed solutions of polymers and methylaminopropyltrimethoxysilane (MAP3), which was modified with N-diazeniumdiolate as an NO donor. In addition, we evaluated their protective effects on hypoxia/reoxygenation (HR) injury in H9c2 cells. The total NO amount released from the resulting MAP3 nanofibers was 1.26 µmol ·mg-1. From the cytotoxicity evaluation of various weights of NO-releasing nanofibers (0 to 2 mg), we selected 1 mg NO-releasing nanofibers for the subsequent experiments. Pre-treatment with NO-releasing nanofibers before hypoxia induction could provide a cytoprotective effect against HR-induced injury in H9c2 cells. The nanofibers could also effectively inhibit the generation of hydrogen peroxide, which was one major contributor to oxidative damage, as well as 8-hydroxyl-2-deoxyguanosine level as an indicator of oxidative DNA damage. In addition, pre-treatment with NO-releasing nano-fibers in a wound model showed wound healing effects similar to those of normal cells. As a result, N-diazeniumdiolate-modified MAP3 nanofibers might protect H9c2 cells from DNA damage by inhibiting the generation of oxidative stress in HR injury. Therefore, we expect that NO-releasing nanofibers could be utilized as a therapeutic strategy for protecting cardiomyocytes from HR injury.

Electrodeposition of SnO2 on FTO and its Application in Planar Heterojunction Perovskite Solar Cells as an Electron Transport Layer.

We report the performance of perovskite solar cells (PSCs) with an electron transport layer (ETL) consisting of a SnO2 thin film obtained by electrochemical deposition. The surface morphology and thickness of the electrodeposited SnO2 films were closely related to electrochemical process conditions, i.e., the applied voltage, bath temperature, and deposition time. We investigated the performance of PSCs based on the SnO2 films. Remarkably, the experimental factors that are closely associated with the photovoltaic performance were strongly affected by the SnO2 ETLs. Finally, to enhance the photovoltaic performance, the surfaces of the SnO2 films were modified slightly by TiCl4 hydrolysis. This process improves charge extraction and suppresses charge recombination.