Localized cell stimulation by nitric oxide using a photoactive porous coordination polymer platform (original) (raw)
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Journal of materials chemistry. B, 2024
The strict dependence of the biological effects of nitric oxide (NO) on its concentration and generation site requires this inorganic free radical to be delivered with precise spatiotemporal control. Lightactivation by suitable NO photoprecursors represents an ideal approach. Developing strategies to activate NO release using long-wavelength excitation light in the therapeutic window (650-1300 nm) is challenging. In this contribution, we demonstrate that NO release by a blue-light activatable NO photodonor (NOPD) with self-fluorescence reporting can be triggered catalytically by the much more biocompatible red light exploiting a supramolecular photosensitization process. Different red-light absorbing photosensitizers (PSs) are co-entrapped with the NOPD within different biocompatible nanocarriers such as Pluronic s micelles, microemulsions and branched cyclodextrin polymers. The intra-carrier photosensitized NO release, involving the lowest, long-lived triplet state of the PS as the key intermediate and its quenching by the NOPD, is competitive with that by molecular oxygen. This allows NO to be released with good efficacy, even under aerobic conditions. Therefore, the adopted general strategy provides a valuable tool for generating NO from an already available NOPD, otherwise activatable with the poorly biocompatible blue light, without requiring any chemical modification and using sophisticated and expensive irradiation sources.
Chemical science, 2018
Nitric oxide (NO) holds great promise as a treatment for cancer hypoxia, if its concentration and localization can be precisely controlled. Here, we report a "Trojan Horse" strategy to provide the necessary spatial, temporal, and dosage control of such drug-delivery therapies at targeted tissues. Described is a unique package consisting of (1) a manganese-nitrosyl complex, which is a photoactivated NO-releasing moiety (photoNORM), plus Nd-doped upconverting nanoparticles (Nd-UCNPs) incorporated into (2) biodegradable polymer microparticles that are taken up by (3) bone-marrow derived murine macrophages. Both the photoNORM [Mn(NO)dpaq ]BPh(dpaq = 2-[,-bis(pyridin-2-yl-methyl)]-amino-'-5-nitro-quinolin-8-yl-acetamido) and the Nd-UCNPs are activated by tissue-penetrating near-infrared (NIR) light at ∼800 nm. Thus, simultaneous therapeutic NO delivery and photoluminescence (PL) imaging can be achieved with a NIR diode laser source. The loaded microparticles are non-toxic t...
A multi-photoresponsive molecular-hybrid for dual-modal photoinactivation of cancer cells
RSC Adv., 2014
We report the design, synthesis, photochemical characterization and biological evaluation of a novel molecular conjugate in which two chromogenic centers, a porphyrin unit and a nitroaniline derivative, are covalently linked through an alkyl spacer. This molecular hybrid can be encapsulated in biocompatible, water soluble polymer nanoparticles where it shows satisfactory fluorescence emission and capability to generate simultaneously the cytotoxic singlet oxygen and nitric oxide upon excitation with visible light. The photoactive nanoassembly can be delivered to A375 melanoma cancer cells where it can be detected through its red fluorescence, and is capable of inducing amplified cell mortality by bimodal action due to the concomitant photoproduction of reactive oxygen and nitrogen oxygen species.
Bioorganic & medicinal chemistry letters, 2015
Photocontrollable NO donors enable precise spatiotemporal release of NO under physiological conditions. We designed and synthesized a novel dimethylnitrobenzene-type NO donor, Flu-DNB-DB, which contains a carbon-carbon double bond in place of the amide bond of previously reported Flu-DNB. Flu-DNB-DB releases NO in response to one-photon activation in the blue wavelength region, and shows a greatly increased two-photon cross-section (δu) at 720nm (Flu-DNB: 0.12GM, Flu-DNB-DB: 0.98GM). We show that Flu-DNB-DB enables precisely controlled intracellular release of NO in response to 950nm pulse laser irradiation for as little as 1s. This near-infrared-light-controllable NO source should be a valuable tool for studies on the biological roles of NO.
ACS Omega, 2019
Devices consisting of polymer disks (PDs) of optically clear or translucent, medical-grade silicone loaded with a new hydrophobic, oxygen-stable, photoactivated nitric oxide-releasing moiety (photoNORM) are described. The photoNORM is the new O-nitrito chromium(III) complex trans-[Cr(PetA)(ONO) 2 ](BF 4) (PetA = 5,14-dimethyl-7,12diphenyl-1,4,8,11-tetraaza-cyclotetradecane), of which the synthesis, X-ray crystal structure, and solution-phase photochemistry are described. Several different commercially available silicone polymers were tested with this photoNORM, and nitric oxide photouncaging with 451 nm light from these systems is compared. In addition, PDs were loaded with the photoNORM and neodymium-sensitized upconverting nanoparticles (Nd-UCNPs). The Nd-UCNPs absorb NIR light at ∼800 nm and activate NO release from the trans-[Cr(PetA)(ONO) 2 ] + cation. The use of such ensembles as implants provides a potential strategy for the in vivo uncaging of NO at physiological targets triggered by tissue-transmitting NIR excitation. Also reported are the X-ray crystal structures of cis-and trans-{Cr(PetA)Cl 2 ]Cl.
Tuning Cellular Biological Functions Through the Controlled Release of NO from a Porous Ti‐MOF
Angewandte Chemie International Edition, 2020
Materials for the controlled release of nitric oxide (NO) are of interest for therapeutic applications. However, to date, many suffer from toxicity and stability issues, as well as poor performance. Herein, we propose a new NO adsorption/ release mechanism through the formation of nitrites on the skeleton of a titanium-based metal-organic framework (MOF) that we named MIP-177, featuring a suitable set of properties for such an application: (i) high NO storage capacity (3 mmol mg À1 solid), (ii) excellent biocompatibility at therapeutic relevant concentrations (no cytotoxicity at 90 mg mL À1 for wound healing) due to its high stability in biological media (< 9 % degradation in 72 hours) and (iii) slow NO release in biological media (% 2 hours for 90 % release). The prospective application of MIP-177 is demonstrated through NO-driven control of mitochondrial respiration in cells and stimulation of cell migration, paving the way for the design of new NO delivery systems for wound healing therapy.
Science and Technology of Advanced Materials, 2011
Nitric oxide (NO) plays a critical role in the regulation of a wide variety of physiological processes. It is a potent inhibitor of platelet adhesion and aggregation, inhibits bacterial adhesion and proliferation, is implicated in mediating the inflammatory response toward implanted devices, plays a role in tumor growth and proliferation, and is a neurotransmitter. Herein, we describe the synthesis and NO-release properties of a modified polydimethylsiloxane that contains S-nitroso-N-acetyl-D-penicillamine covalently attached to the cross-linking agent (SNAP-DMS). Light from a C503B-BAN-CY0C0461 light-emitting diode (470 nm) was used as an external trigger to allow precise control over level and duration of NO release ranging from a surface flux of zero to approximately 3.5 × 10 −10 mol cm −2 min −1. SNAP-PDMS films stored in the dark released NO after 297 days, indicating the long-term stability of SNAP-PDMS.