Nitric Oxide-Loaded Antimicrobial Polymer for the Synergistic Eradication of Bacterial Biofilm

Namivandi-Zangeneh, Rashin; Sadrearhami, Zahra; Bagheri, Ali; Sauvage-Nguyen, Maeva; Ho, Kaitlyn; Kumar, Naresh; Wong, Edgar H. H.; Boyer, Cyrille

doi:10.1021/acsmacrolett.8b00190

Cited by 86 publications

(82 citation statements)

References 44 publications

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“…25 Co-delivery of NO with a drug has proven effective in decreasing the required therapeutic concentration of the drug alone. 52–54 With this in mind, we investigated the ability of CD-NONOates to deliver both NO and a hydrophobic drug. As a proof-of-concept, promethazine (PM) was selected as a model hydrophobic drug in our study.…”

Section: Resultsmentioning

confidence: 99%

Nitric Oxide-Releasing Cyclodextrins

2018

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A series of secondary amine-modified cyclodextrin (CD) derivatives were synthesized with diverse exterior terminal groups (i.e., hydroxyl, methyl, methoxyl, and primary amine). Subsequent reaction with nitric oxide (NO) gas under alkaline conditions yielded N-diazeniumdiolate-modified CD derivatives. Adjustable NO payloads (0.6–2.4 µmol/mg) and release half-lives (0.7–4.2 h) were achieved by regulating both the amount of secondary amine precursors and the functional groups around the NO donor. The bactericidal action of these NO-releasing cyclodextrin derivatives was evaluated against Pseudomonas aeruginosa, a Gram-negative pathogen with antibacterial activity proving dependent on both the NO payload and exterior modification. Materials containing a high density of NO donors or primary amines exhibited the greatest ability to eradicate P. aeruginosa. Of the materials prepared, only the primary amine-terminated hepta-substituted CD derivatives exhibited toxicity against mammalian L929 mouse fibroblast cells. The NO donor-modified CD was also capable of delivering promethazine, a hydrophobic drug, thus demonstrating potential as a dual-drug releasing therapeutic.

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Section: Resultsmentioning

confidence: 99%

Nitric Oxide-Releasing Cyclodextrins

2018

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“…Although many of the NONOate-based polymeric NO donors were obtained by the functionalization of secondary amine-containing polymers, aliphatic primary amines can also be transformed into NONOate derivatives as well. Recently, a statistical ternary copolymer containing primary amine residues was synthesized (Namivandi-Zangeneh et al, 2018). The primary amine moieties were converted into NONOates in the presence of NO gas under high pressure.…”

Section: N-diazeniumdiolate (Nonoate)-based Polymeric No Donorsmentioning

confidence: 99%

Nitric Oxide (NO)-Releasing Macromolecules: Rational Design and Biomedical Applications

Cheng

Shen

et al. 2019

Front. Chem.

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Nitric oxide (NO) has been recognized as a ubiquitous gaseous transmitter and the therapeutic potential has nowadays received increasing interest. However, NO cannot be easily directly administered due to its high reactivity in air and high concentration-dependent physiological roles. As such, a plethora of NO donors have been developed that can reversibly store and release NO under specific conditions. To enhance the stability and modulate the NO release profiles, small molecule-based NO donors were covalently linked to polymeric scaffolds, rendering them with multifunctional integration, prolonged release durations, and optimized therapeutic outcomes. In this minireview, we highlight the recent achievements of NO-releasing macromolecules in terms of chemical design and biomedical applications. We hope that more efforts could be devoted to this emerging yet promising field.

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“…In innate immunity, NO exerts its antimicrobial effect and acts as a toxic defense molecule against infectious organisms [115,116,117]. NO antimicrobial polymers have recently been developed and shown to be effective for various antimicrobial applications, including the eradication of biofilms and therapy for Staphylococcus aureus and other antibiotic-resistant skin infections [118,119,120].…”

Section: Nitric Oxide and Cancermentioning

confidence: 99%

Nitric Oxide-Mediated Enhancement and Reversal of Resistance of Anticancer Therapies

Hays

Bonavida

2019

Antioxidants

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In the last decade, immune therapies against human cancers have emerged as a very effective therapeutic strategy in the treatment of various cancers, some of which are resistant to current therapies. Although the clinical responses achieved with many therapeutic strategies were significant in a subset of patients, another subset remained unresponsive initially, or became resistant to further therapies. Hence, there is a need to develop novel approaches to treat those unresponsive patients. Several investigations have been reported to explain the underlying mechanisms of immune resistance, including the anti-proliferative and anti-apoptotic pathways and, in addition, the increased expression of the transcription factor Yin-Yang 1 (YY1) and the programmed death ligand 1 (PD-L1). We have reported that YY1 leads to immune resistance through increasing HIF-1α accumulation and PD-L1 expression. These mechanisms inhibit the ability of the cytotoxic T-lymphocytes to mediate their cytotoxic functions via the inhibitory signal delivered by the PD-L1 on tumor cells to the PD-1 receptor on cytotoxic T-cells. Thus, means to override these resistance mechanisms are needed to sensitize the tumor cells to both cell killing and inhibition of tumor progression. Treatment with nitric oxide (NO) donors has been shown to sensitize many types of tumors to chemotherapy, immunotherapy, and radiotherapy. Treatment of cancer cell lines with NO donors has resulted in the inhibition of cancer cell activities via, in part, the inhibition of YY1 and PD-L1. The NO-mediated inhibition of YY1 was the result of both the inhibition of the upstream NF-κB pathway as well as the S-nitrosylation of YY1, leading to both the downregulation of YY1 expression as well as the inhibition of YY1-DNA binding activity, respectively. Also, treatment with NO donors induced the inhibition of YY1 and resulted in the inhibition of PD-L1 expression. Based on the above findings, we propose that treatment of tumor cells with the combination of NO donors, at optimal noncytotoxic doses, and anti-tumor cytotoxic effector cells or other conventional therapies will result in a synergistic anticancer activity and tumor regression.

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Nitric Oxide-Loaded Antimicrobial Polymer for the Synergistic Eradication of Bacterial Biofilm

Cited by 86 publications

References 44 publications

Nitric Oxide-Releasing Cyclodextrins

Nitric Oxide-Releasing Cyclodextrins

Nitric Oxide (NO)-Releasing Macromolecules: Rational Design and Biomedical Applications

Nitric Oxide-Mediated Enhancement and Reversal of Resistance of Anticancer Therapies

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