Delivery of nitric oxide with a pH-responsive nanocarrier for the treatment of renal fibrosis

Lee, Tsung-Ying; Lu, Hung‐Hsun; Cheng, Hongyan; Huang, Hsi‐Chien; Tsai, Yun‐Jen; Chang, I-Hsiang; Tu, C.Y.; Chung, Chieh-Wei; Lu, Tsai‐Te; Peng, Chi‐How; Chen, Yunching

doi:10.1016/j.jconrel.2022.12.059

Cited by 12 publications

(6 citation statements)

References 48 publications

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“…Recently, synthetic DNICs have emerged as a type of novel and effective prodrug for controlled delivery of NO and NO-related biomedical applications. − In particular, thiolate-bridged dinuclear {Fe(NO) 2 } 9 -{Fe(NO) 2 } 9 DNIC [(NO) 2 Fe(μ-SCH 2 CH 2 OH) 2 Fe(NO) 2 ] displayed in vitro anti-inflammation activity against LPS-activated microglial BV-2 cells and in vivo therapeutic efficacy for the recovery of impaired cognitive ability of aging mice with metabolic syndrome . Alternatively, {Fe(NO) 2 } 9 -{Fe(NO) 2 } 9 DNIC 1 was explored for efficient nitroxylation of Fe III -porphyrin centers in Fe(TPP)Cl and met-myoglobin, while the in vitro and in vivo investigations are forthcoming.…”

Section: Conclusion and Commentsmentioning

confidence: 99%

“…In addition to providing the biomimetic insights into Fe-NO biology, recently, biomimetic dinitrosyl iron complexes (DNICs) were explored for controlled delivery of NO and activation of NO-related biomedical applications. − Despite the reported study of interactions between {Fe(NO) 2 } 10 DNICs [(NO) 2 Fe(L)] (L = TMEDA, PMDTA, and 2,9-dimethyl-1,10-phenanthroline) and O 2 , − transformation of DNICs under (simulated) inflammatory conditions (i.e., presence of O 2 – ) remains elusive. Consequently, the reactions of dinuclear {Fe(NO) 2 } 9 -{Fe(NO) 2 } 9 DNICs [(NO) 2 Fe(μ- Me Pyr) 2 Fe(NO) 2 ] ( 1 ) and [(NO) 2 Fe(μ-SEt) 2 Fe(NO) 2 ] ( 3 ), respectively, toward O 2 – are investigated in this study to understand the ligand control over the reactivity of DNICs.…”

Section: Introductionmentioning

confidence: 99%

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Ligand Control of Dinitrosyl Iron Complexes for Selective Superoxide-Mediated Nitric Oxide Monooxygenation and Superoxide–Dioxygen Interconversion

Liao,

Tseng,

Cheng

et al. 2023

J. Am. Chem. Soc.

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Through nitrosylation of [Fe–S] proteins, or the chelatable iron pool, a dinitrosyl iron unit (DNIU) [Fe(NO)2] embedded in the form of low-molecular-weight/protein-bound dinitrosyl iron complexes (DNICs) was discovered as a metallocofactor assembled under inflammatory conditions with elevated levels of nitric oxide (NO) and superoxide (O2 –). In an attempt to gain biomimetic insights into the unexplored transformations of the DNIU under inflammation, we investigated the reactivity toward O2 – by a series of DNICs [(NO)2Fe(μ-MePyr)2Fe(NO)2] (1) and [(NO)2Fe(μ-SEt)2Fe(NO)2] (3). During the superoxide-induced conversion of DNIC 1 into DNIC [(K-18-crown-6-ether)2(NO2)][Fe(μ-MePyr)4(μ-O)2(Fe(NO)2)4] (2-K-crown) and a [Fe3+(MePyr) x (NO2) y (O) z ] n adduct, stoichiometric NO monooxygenation yielding NO2 – occurs without the transient formation of peroxynitrite-derived •OH/•NO2 species. To study the isoelectronic reaction of O2(g) and one-electron-reduced DNIC 1, a DNIC featuring an electronically localized {Fe(NO)2}9-{Fe(NO)2}10 electronic structure, [K-18-crown-6-ether][(NO)2Fe(μ-MePyr)2Fe(NO)2] (1-red), was successfully synthesized and characterized. Oxygenation of DNIC 1-red leads to the similar assembly of DNIC 2-K-crown, of which the electronic structure is best described as paramagnetic with weak antiferromagnetic coupling among the four S = 1/2 {FeIII(NO – )2}9 units and S = 5/2 Fe3+ center. In contrast to DNICs 1 and 1-red, DNICs 3 and [K-18-crown-6-ether][(NO)2Fe(μ-SEt)2Fe(NO)2] (3-red) display a reversible equilibrium of “3 + O2 – ⇋ 3-red + O2(g)”, which is ascribed to the covalent [Fe(μ-SEt)2Fe] core and redox-active [Fe(NO)2] unit. Based on this study, the supporting/bridging ligands in dinuclear DNIC 1/3 (or 1-red/3-red) control the selective monooxygenation of NO and redox interconversion between O2 – and O2 during reaction with O2 – (or O2).

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Section: Conclusion and Commentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ligand Control of Dinitrosyl Iron Complexes for Selective Superoxide-Mediated Nitric Oxide Monooxygenation and Superoxide–Dioxygen Interconversion

Liao,

Tseng,

Cheng

et al. 2023

J. Am. Chem. Soc.

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“…NO donor molecules loaded in pH-responsive micelles were designed for payload release under acidic conditions, including areas of ongoing tissue damage as well as intracellularly, within the cell lysosome. These nanoparticles had increased uptake in fibrotic kidneys and significantly reduced fibrosis [16 ▪ ]. Several nanoparticle formulations have shown promise in the kidney by repurposing antifibrotics that were already approved for other indications.…”

Section: Chronic Kidney Diseasementioning

confidence: 99%

Nanomedicine in kidney disease

Bishop

Sharma

Scott

2023

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewThe pathophysiological understanding of kidney-related disorders has profoundly increased; however, tissuespecific and cell-specific treatments in this field remain scarce. Advances in nanomedicine enable alteration of pharmacokinetics and targeted treatments improving efficiency and reducing toxicity. This review addresses recent developments of nanocarriers used for various purposes in the broad field of kidney disease, which may pave a path to new therapeutic and diagnostic solutions employing nanomedicine. Recent findingsControlled delivery of antiproliferative medications enables improved treatment of polycystic kidney disease and fibrosis. Directed anti-inflammatory treatment mitigated glomerulonephritis and tubulointerstitial nephritis. Multiple injury pathways in AKI have been targeted, with therapeutic solutions for oxidative stress, mitochondrial dysfunction, local inflammation and improving self-repair mechanisms. In addition to such treatment development, noninvasive early detection methods (minutes after ischemic insult) have been demonstrated as well. Sustained release of therapies that reduce ischemia--reperfusion injury as well as new aspects for immunosuppression bring hope to improving kidney transplant outcomes. The latest breakthroughs in gene therapy are made achievable by engineering the targeted delivery of nucleic acids for new treatments of kidney disease. SummaryRecent advances in nanotechnology and pathophysiological understanding of kidney diseases show potential for translatable therapeutic and diagnostic interventions in multiple etiologies of kidney disease.

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“…As a ubiquitous gasotransmitter, nitric oxide (NO) can activate the expression of HO-1 and promote cytoprotection toward vascular endothelium. − Recently, biomimetic dinitrosyl iron complexes (DNICs) were explored as a prodrug for controlled delivery of NO and treatments of cancers, − diabetic/bacteria-infected wound healing, − hypertension, neurodegenerative disorders, − and tissue engineering. − In addition to the potential biomedical applications, systematic reviews on bioinorganic and coordination chemistry, ,, synthetic methodology, , and electronic structure study of biomimetic DNICs were also reported . As opposed to the other reported NO-delivery reagents, DNICs [(NO) 2 Fe(μ-SR) 2 Fe(NO) 2 ] feature a unique O 2 -induced mechanism for the release of NO, of which the kinetics are modulated by the side chain of bridging thiolate ligands. ,,,,, In addition, rapid and reversible binding of DNIC [(NO) 2 Fe(μ-SCH 2 CH 2 OH) 2 Fe(NO) 2 ] toward the protein-derived cysteine residues in gastrointestinal mucin and serum albumin occurs to promote the assembly of protein-bound DNIC [(NO) 2 Fe(SR)(S Cys‑protein )] n − .…”

Section: Introductionmentioning

confidence: 99%

“… 36 − 41 Recently, biomimetic dinitrosyl iron complexes (DNICs) were explored as a prodrug for controlled delivery of NO and treatments of cancers, 42 − 44 diabetic/bacteria-infected wound healing, 45 − 47 hypertension, 48 neurodegenerative disorders, 49 − 53 and tissue engineering. 54 − 59 In addition to the potential biomedical applications, 51 systematic reviews on bioinorganic and coordination chemistry, 52 , 60 , 61 synthetic methodology, 62 , 63 and electronic structure study of biomimetic DNICs were also reported. 64 As opposed to the other reported NO-delivery reagents, DNICs [(NO) 2 Fe(μ-SR) 2 Fe(NO) 2 ] feature a unique O 2 -induced mechanism for the release of NO, of which the kinetics are modulated by the side chain of bridging thiolate ligands.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic and Kinetic Insights into Cellular Uptake of Biomimetic Dinitrosyl Iron Complexes and Intracellular Delivery of NO for Activation of Cytoprotective HO-1

Chiu,

Chau Fang,

Chen

et al. 2024

JACS Au

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Dinitrosyl iron unit (DNIU), [Fe(NO) 2 ], is a natural metallocofactor for biological storage, delivery, and metabolism of nitric oxide (NO). In the attempt to gain a biomimetic insight into the natural DNIU under biological system, in this study, synthetic dinitrosyl iron complexes (DNICs) [(NO) 2 Fe(μ-SCH 2 CH 2 COOH) 2 Fe(NO) 2 ] (DNIC−COOH) and [(NO) 2 Fe(μ-SCH 2 CH 2 COOCH 3 ) 2 Fe(NO) 2 ] (DNIC−COOMe) were employed to investigate the structure−reactivity relationship of mechanism and kinetics for cellular uptake of DNICs, intracellular delivery of NO, and activation of cytoprotective heme oxygenase (HO)-1. After rapid cellular uptake of dinuclear DNIC−COOMe through a thiol-mediated pathway (t max = 0.5 h), intracellular assembly of mononuclear DNIC [(NO) 2 Fe(SR)-(S Cys )] n− /[(NO) 2 Fe(SR)(S Cys-protein )] n− occurred, followed by O 2 -induced release of free NO (t max = 1−2 h) or direct transfer of NO to soluble guanylate cyclase, which triggered the downstream HO-1. In contrast, steady kinetics for cellular uptake of DNIC− COOH via endocytosis (t max = 2−8 h) and for intracellular release of NO (t max = 4−6 h) reflected on the elevated activation of cytoprotective HO-1 (∼50−150-fold change at t = 3−10 h) and on the improved survival of DNIC−COOH-primed mesenchymal stem cell (MSC)/human corneal endothelial cell (HCEC) under stressed conditions. Consequently, this study unravels the bridging thiolate ligands in dinuclear DNIC−COOH/DNIC−COOMe as a switch to control the mechanism, kinetics, and efficacy for cellular uptake of DNICs, intracellular delivery of NO, and activation of cytoprotective HO-1, which poses an implication on enhanced survival of postengrafted MSC for advancing the MSC-based regenerative medicine.

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Delivery of nitric oxide with a pH-responsive nanocarrier for the treatment of renal fibrosis

Cited by 12 publications

References 48 publications

Ligand Control of Dinitrosyl Iron Complexes for Selective Superoxide-Mediated Nitric Oxide Monooxygenation and Superoxide–Dioxygen Interconversion

Ligand Control of Dinitrosyl Iron Complexes for Selective Superoxide-Mediated Nitric Oxide Monooxygenation and Superoxide–Dioxygen Interconversion

Nanomedicine in kidney disease

Mechanistic and Kinetic Insights into Cellular Uptake of Biomimetic Dinitrosyl Iron Complexes and Intracellular Delivery of NO for Activation of Cytoprotective HO-1

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