Targeted Nitric Oxide Delivery by Supramolecular Nanofibers for the Prevention of Restenosis After Arterial Injury

Bahnson, Edward Moreira; Kassam, Hussein A.; Moyer, Tyson J.; Jiang, Wulin; Morgan, Courtney E.; Vercammen, Janet M.; Jiang, Qun; Flynn, Megan; Stupp, Samuel I.; Kibbe, Melina R.

doi:10.1089/ars.2015.6363

Cited by 51 publications

(74 citation statements)

References 54 publications

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“…Based upon our previously published work, the duration of binding of the T‐AuNP appears to be sufficient to have a durable inhibition of neointimal hyperplasia (Bahnson et al. ). Additionally, a benefit of this construct is that repeat intravenous dosing of the T‐AuNPs could extend this therapeutic window, which should be sufficient to have a beneficial clinical impact on vascular repair following arterial injury.…”

Section: Discussionmentioning

confidence: 98%

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Systemically administered collagen-targeted gold nanoparticles bind to arterial injury following vascular interventions

et al. 2017

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Surgical and endovascular therapies for severe atherosclerosis often fail due to the development of neointimal hyperplasia and arterial restenosis. Our objective was to synthesize, characterize, and evaluate the targeting specificity and biocompatibility of a novel systemically injected nanoparticle. We hypothesize that surface‐functionalization of gold nanoparticles (AuNPs) with a collagen‐targeting peptide will be biocompatible and target specifically to vascular injury. 13 nm AuNPs were surface functionalized with a peptide‐molecular fluorophore and targeted to collagen (T‐AuNP) or a scrambled peptide sequence (S‐AuNP). After rat carotid artery balloon injury and systemic injection of T‐AuNP or S‐AuNP, arteries and organs were harvested and assessed for binding specificity and biocompatibility. The T‐AuNP bound with specificity to vascular injury for a minimum of 24 h. No significant inflammation was evident locally at arterial injury or systemically in major organs. The T‐AuNP did not impact endothelial cell viability or induce apoptosis at the site of injury in vivo. No major changes were evident in hepatic or renal blood chemistry profiles. Herein, we synthesized a biocompatible nanoparticle that targets to vascular injury following systemic administration. These studies demonstrate proof‐of‐principle and serve as the foundation for further T‐AuNP optimization to realize systemic, targeted delivery of therapeutics to the sites of vascular injury.

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Section: Discussionmentioning

confidence: 98%

“…()in and used in other studies from our laboratory to target vascular injury (Bahnson et al. ; Chan et al. , ; Moyer et al.…”

Section: Discussionmentioning

confidence: 99%

Systemically administered collagen-targeted gold nanoparticles bind to arterial injury following vascular interventions

et al. 2017

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“…This notion is consistent with the beneficial effect of GSNOR deficiency on cardiac repair [30] and ventricular systolic and diastolic function and tissue oxygenation [31] in a mouse model of myocardial injury. Similarly, pharmacological inhibition of GSNOR reduces vascular resistance and augments blood flow-mediated vasodilation in hypertensive rats [32], while targeted S -nitrosylation reduces neointimal hyperplasia and infarct size in animal models of carotid artery injury [33] and ischemia-reperfusion injury [34]. S -nitrosylation is thought to provide cardioprotection, in part, by modulating the activity of target proteins and by preventing the irreversible oxidation of critical cysteine residues that may occur with oxidative stress [35].…”

Section: Discussionmentioning

confidence: 99%

Transnitrosylation: A Factor in Nitric Oxide–Mediated Penile Erection

Musicki¹,

Lagoda²,

Goetz³

et al. 2016

The Journal of Sexual Medicine

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Introduction Nitric oxide (NO) signaling can be mediated not only through classical cGMP, but also through S-nitrosylation. The impact of S-nitrosylation on erectile function and in NO regulation and oxidative stress in the penis, however, remains poorly understood. Aims To characterize the role of GSNOR, a major regulator of S-nitrosylation homeostasis, on erection physiology and on eNOS function and oxidative/nitrosative stress in the penis. Materials and Methods Adult GSNOR-deficient and WT mice were used. Erectile function was assessed in response to electrical stimulation of the cavernous nerve. Total NO in penile homogenates was measured by Griess reaction. Protein S-nitrosylation, endothelial NO synthase (eNOS) phosphorylation on Ser-1177 (positive regulatory site), eNOS uncoupling, and markers of oxidative stress (4-hydroxy-2-nonenal [4-HNE], malondialdehyde, and nitrotyrosine) in the penis were measured by Western blot. Main outcome measures Erectile function, eNOS function and oxidative stress in the penis of GSNOR-deficient mice. Results Erectile function was intact in GSNOR-deficient mice. Total S-nitrosylated proteins were increased (p<0.05) in the GSNOR−/− compared to WT mouse penis. While eNOS phosphorylation on Ser-1177 did not differ between the GSNOR−/− and WT mouse penis at baseline, electrical stimulation of the cavernous nerve increased (p<0.05) P-eNOS in the WT mouse penis, but failed to increase P-eNOS in the GSNOR−/− mouse penis. Total NO production was decreased (p<0.05), while eNOS uncoupling, 4-HNE, malondialdehyde, and nitrotyrosine were increased (p<0.05) in the GSNOR-deficient mouse penis compared to that of WT mice. Conclusion Transnitrosylation mechanisms play an important role in regulating NO bioactivity in the penis. Deficiency of GSNOR leads to eNOS dysfunction and increased oxidative damage, suggesting that homeostatic eNOS function in the penis is governed by transnitrosylation.

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“…In a similar manner, nitric oxide was also delivered for the prevention of restenosis. 218 A number of other hydrogelators have also been applied to various settings by conjugating different drug cargos. For example the formation of an antibacterial olsalazine hydrogel 219 and a bortezomib-based hydrogel for local cancer treatment.…”

Section: Small Molecule Sapdsmentioning

confidence: 99%

Self-assembling prodrugs

et al. 2017

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Covalent modification of therapeutic compounds is a clinically proven strategy to devise prodrugs with enhanced treatment efficacies. This prodrug strategy relies on modified drugs that possess advantageous pharmacokinetic properties and administration routes over their parent drug. Self-assembling prodrugs represent an emerging class of therapeutic agents capable of spontaneously associating into well-defined supramolecular nanostructures in aqueous solutions. The self-assembly of prodrugs expands the functional space of conventional prodrug design, providing a possible pathway to more effective therapies as the assembled nanostructure possesses distinct physicochemical properties that can be tailored to specific administration routes and disease treatment. In this review, we will discuss the various types of self-assembling prodrugs in development, providing an overview of the methods used to control their structure and function and, ultimately, our perspective on their current and future potential.

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Targeted Nitric Oxide Delivery by Supramolecular Nanofibers for the Prevention of Restenosis After Arterial Injury

Cited by 51 publications

References 54 publications

Systemically administered collagen-targeted gold nanoparticles bind to arterial injury following vascular interventions

Systemically administered collagen-targeted gold nanoparticles bind to arterial injury following vascular interventions

Transnitrosylation: A Factor in Nitric Oxide–Mediated Penile Erection

Self-assembling prodrugs

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