Nitric Oxide Releasing Nanomaterials for Cancer Treatment: Current Status and Perspectives

Seabra, Amedea B.; Lima, Renata de; Calderón, Marcelo

doi:10.2174/1568026615666150108122918

Cited by 56 publications

(30 citation statements)

References 85 publications

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“…This has inspired the development of molecular NO‐donors able to uncage NO from tailored molecular and macromolecular scaffolds either spontaneously or upon application of suitable stimuli ( i. e . temperature, pH, light) . However, the full therapeutic potential of NO strictly relies on its precise spatiotemporal control .…”

Section: Introductionmentioning

confidence: 99%

A High‐Performing Metal‐Free Photoactivatable Nitric Oxide Donor with a Green Fluorescent Reporter

et al. 2020

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We report herein a novel nitric oxide (NO) donor activatable by visible blue light with an in‐built green fluorescence reporter. This NO photodonor, based on the amino‐nitro‐benzofurazan chromogenic skeleton, releases NO in solution with a quantum yield ΦNO=0.15 which increases up to 0.80 in Pluronic® micelles, the largest values ever reported for nonmetal‐containing NO donors activatable by visible light. Besides, the large contrast between the fluorescence emission of the chromogenic moiety after and before the NO release (>10) permits the easy and in real‐time quantification of the amount of NO released, without the addition of external fluorescent probes. This NO photodonor can also be effectively entrapped in a Pluronic‐based thermoresponsive hydrogel with excellent preservation of its photochemical and photophysical behaviour. These properties, together with the facile synthetic procedure, make the present compound an intriguing candidate for fundamental and potential applicative research studies where spatiotemporally regulated NO delivery is required.

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Section: Introductionmentioning

confidence: 99%

A High‐Performing Metal‐Free Photoactivatable Nitric Oxide Donor with a Green Fluorescent Reporter

et al. 2020

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“…[18] To increase their bioavailability and in vivo stability, low molecular weight molecules capable of acting as NO donors, such as S-nitrosothiols (RSNOs), have been developed. [19] Considering that NO-releasing polymeric nanomaterials are emerging as a promising strategy in cancer chemotherapy, [20] biocompatible chitosan nanoparticles (CS) were synthesized and used to encapsulate low molecular weight mercaptosuccinic acid (MSA), a thiol-containing small molecule. Free thiol groups on mercaptosuccinic chitosan nanoparticles (MSA-CS) were nitrosated to form S-nitroso-MSA-containing chitosan nanoparticles (S-nitroso-MSA-CS).…”

Section: Introductionmentioning

confidence: 99%

Antitumor Potential of S-Nitrosothiol-Containing Polymeric Nanoparticles against Melanoma

et al. 2018

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Melanoma is a malignant proliferative disease originated from melanocyte transformations, which are characterized by a high metastatic rate and mortality. Advances in Nanotechnology have provided useful new approaches and tools for antitumor chemotherapy. The aim of this study was to investigate the molecular mechanisms underlying chitosan nanoparticles containing S-nitrosomercaptosuccinic acid ( S-nitroso-MSA-CS) induced cytotoxicity in melanoma cells. S-Nitroso-MSA-CS induced concentration-dependent cell death against B16-F10 tumor cells, whereas non-nitroso nanoparticles (CS or MSA-CS) did not induce significant cytotoxicity. Additionally, melanoma cells were more sensitive to cell death than normal melanocytes. S-Nitroso-MSA-CS-induced cytotoxicity exhibited features of caspase-dependent apoptosis, and it was associated with oxidative stress, characterized by increased mitochondrial superoxide production and oxidation of protein thiol groups. In addition, tyrosine nitration and cysteine S-nitrosylation of amino acid residues in cellular proteins were observed. The potential use of these nanoparticles in antitumor chemotherapy of melanoma is discussed.

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“…Although many NO-based small molecules were developed as selective and potent anticancer agents, there is increasing interest in developing NO-releasing nanomaterials that include polymeric nanoparticles (8)(9)(10), dendritic polymers (11), liposomes (12), and silica nanoparticles (13). Compared with classical NO donors, the NO-releasing nanomaterials load a higher level of NO onto the high surface area and deliver NO to the desired sites, but it also increases the stability of the NO donor, which avoids the side effects of the off-target release of NO.…”

Section: Introductionmentioning

confidence: 99%

Anti-CD24 Antibody–Nitric Oxide Conjugate Selectively and Potently Suppresses Hepatic Carcinoma

et al. 2019

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Nitric oxide (NO) has a wide range of potential applications in tumor therapy. However, a targeted delivery system for NO donors has remained elusive, creating a bottleneck that limits its druggability. The antibody-drug conjugate (ADC) is a targeted drug delivery system composed of an antibody linked to an active cytotoxic drug. This design may compensate for the weak targeting ability and various biological functions of the NO donor. In this study, we designed the NO donor HL-2, which had a targeted, cleaved disulfide bond and an attachable maleimide terminal. We conjugated HL-2 with an antibody that targeted CD24 through a thioether bond to generate an ADC-like immunoconjugate, antibody-nitric oxide conjugate (ANC), which we named HN-01. HN-01 showed efficient internalization and significantly increased the release of NO in hepatic carcinoma cells in vitro. HN-01 induced apoptosis of tumor cells and suppressed tumor growth in hepatic carcinomabearing nude mice through antibody-dependent co-toxicity; HN-01 also increased NO levels in tumor cells. Collectively, this study expands the concept of ADC and provides an innovative NO donor and ANC to address current challenges in targeted delivery of NO. This new inspiration for an ANC design can also be used in future studies for other molecules with intracellular targets.Significance: This study is the first to expand the concept of ADC with an antibody-nitric oxide conjugate that suppresses hepatic carcinoma in vitro and in vivo.

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Nitric Oxide Releasing Nanomaterials for Cancer Treatment: Current Status and Perspectives

Cited by 56 publications

References 85 publications

A High‐Performing Metal‐Free Photoactivatable Nitric Oxide Donor with a Green Fluorescent Reporter

A High‐Performing Metal‐Free Photoactivatable Nitric Oxide Donor with a Green Fluorescent Reporter

Antitumor Potential of S-Nitrosothiol-Containing Polymeric Nanoparticles against Melanoma

Anti-CD24 Antibody–Nitric Oxide Conjugate Selectively and Potently Suppresses Hepatic Carcinoma

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