Light-Activated Biodegradable Covalent Organic Framework-Integrated Heterojunction for Photodynamic, Photothermal, and Gaseous Therapy of Chronic Wound Infection.

Chronic wound healing, impeded by bacterial infections and drug resistance, poses a threat to global human health. Antibacterial phototherapy is an effective way to fight microbial infection without causing drug resistance. Covalent organic frameworks (COFs) are a class of highly crystalline functional porous carbon-based materials composed of light atoms (e.g., carbon, nitrogen, oxygen, and borane), showing potential applications in the biomedical field. Herein, we constructed porphyrin-based COF nanosheets (TP-Por CON) for synergizing photodynamic and photothermal therapy under red light irradiation (e.g., 635 nm). Moreover, a nitric oxide (NO) donor molecule, BNN6, was encapsulated into the pore volume of the crystalline porous framework structure to moderately release NO triggered by red light irradiation for realizing gaseous therapy. Therefore, we successfully synthesized a novel TP-Por CON@BNN6-integrated heterojunction for thoroughly killing Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus in vitro. Our research identified that TP-Por CON@BNN6 has favorable biocompatibility and biodegradability, low phototoxicity, anti-inflammatory properties, and excellent mice wound healing ability in vivo. This study indicates that the TP-Por CON@BNN6-integrated heterojunction with multifunctional properties provides a potential strategy for COF-based gaseous therapy and microorganism-infected chronic wound healing.

Review of a Potential Novel Approach for Erectile Dysfunction: Light-Controllable Nitric Oxide Donors and Nanoformulations.

INTRODUCTION: Nitric oxide (NO) is known as the key factor involved in initiating and maintaining an erection. Therefore, NO supplementation may be a target for erectile dysfunction. However, the use of NO donors carries the risk of systemic side effects. Recently, novel NO donors, such as a light-controllable NO donor or NO donor in nanoparticles, have been developed. In this review, we introduce such novel compounds and methods. AIM: To review light-controllable and nanotechnological NO donors for the treatment of erectile dysfunction. METHODS: We conducted a review of relevant articles via PubMed in December 2018. MAIN OUTCOME MEASURES: In this study, we reviewed novel NO donors, such as light-controllable NO donors and nanotechnological NO donors. RESULTS: Some light-controllable NO donors have been already reported. A light-controllable NO donor without metal has also been recently developed. Light-controllable NO donors and light irradiation can control the release of NO spatiotemporally. In an isometric tension study, a relaxing response of the aortic tissue and penile corpus cavernosum was observed under light irradiation with a light-controllable NO donor. In addition, the effects of nanoparticles and nanoemulsions containing sodium nitrate on erectile function have been reported. The nanoformulation containing an NO donor can likely be absorbed percutaneously and, thus, enhance erectile function. CONCLUSIONS: A light-controllable NO donor might be useful for treating erectile dysfunction because light irradiation is a convenient method to be applied for patients. However, light permeability might be an issue that needs to be solved. Nanoformulation is also likely to be a useful, non-invasive approach. The application of these procedures and compounds may help in the development of future treatments for erectile dysfunction. Hotta Y, Kataoka T, Taiki Mori T, et al. Review of a Potential Novel Approach for Erectile Dysfunction: Light-Controllable Nitric Oxide Donors and Nanoformulations. Sex Med Rev 2020;8:297-302.

Photoactive ruthenium nitrosyls as NO donors: how to sensitize them toward visible light.

Nitric oxide (NO) can induce apoptosis (programmed cell death) at micromolar or higher doses. Although cell death via NO-induced apoptosis has been studied quite extensively, the targeted delivery of such doses of NO to infected or malignant tissues has not been achieved. The primary obstacle is indiscriminate NO release from typical systemic donors such as glycerin trinitrate: once administered, the drug travels throughout the body, and NO is released through a variety of enzymatic, redox, and pH-dependent pathways. Photosensitive NO donors have the ability to surmount this difficulty through the use of light as a localized stimulus for NO delivery. The potential of the method has prompted synthetic research efforts toward new NO donors for use as photopharmaceuticals in the treatment of infections and malignancies. Over the past few years, we have designed and synthesized several metal nitrosyls (NO complexes of metals) that rapidly release NO when exposed to low-power (milliwatt or greater) light of various wavelengths. Among them, the ruthenium nitrosyls exhibit exceptional stability in biological media. However, typical ruthenium nitrosyls release NO upon exposure to UV light, which is hardly suitable for phototherapy. By following a few novel synthetic strategies, we have overcome this problem and synthesized a variety of ruthenium nitrosyls that strongly absorb light in the 400-600-nm range and rapidly release NO under such illumination. In this Account, we describe our progress in designing photoactive ruthenium nitrosyls as visible-light-sensitive NO donors. Our research has shown that alteration of the ligands, in terms of (i) donor atoms, (ii) extent of conjugation, and (iii) substituents on the ligand frames, sensitizes the final ruthenium nitrosyls toward visible light in a predictable fashion. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations provide guidance in this "smart design" of ligands. We have also demonstrated that direct attachment of dye molecules as light-harvesting antennas also sensitize ruthenium nitrosyls to visible light, and TDDFT calculations provide insight into the mechanisms of sensitization by this technique. The fluorescence of the dye ligands makes these NO donors "trackable" within cellular matrices. Selected ruthenium nitrosyls have been used to deliver NO to cellular targets to induce apoptosis. Our open-design strategies allow the isolation of a variety of these ruthenium nitrosyls, depending on the choices of the ligand frames and dyes. These designed nitrosyls will thus be valuable in the future endeavor of synthesizing novel pharmaceuticals for phototherapy.