Dataset Information

Extended Nitric Oxide-Releasing Polyurethanes via S-Nitrosothiol-Modified Mesoporous Silica Nanoparticles.

ABSTRACT: S-Nitrosothiol (RSNO)-modified mesoporous silica nanoparticles (MSNs) were doped into polyurethane (PU) to achieve extended NO-releasing coatings. Parameters influencing the synthesis of RSNO-functionalized nitric oxide (NO)-releasing MSNs were evaluated to elucidate the impact of pore structure on NO release characteristics. The porous particles were characterized as having larger NO payloads and longer NO release durations than those of nonporous particles, a feature attributed to the recombination of the NO radical in confined intraporous microenvironments. NO release kinetics, particle leaching, and thermal stability of the RSNO-modified MSNs dispersed in PU were evaluated as a function of PU structure to determine the feasibility of preparing a range of NO-releasing polymers for biomedical device-coating applications. The NO release kinetics from the PUs proved to be highly extended (>30 d) and consistent over a range of PU properties. Furthermore, RSNO-modified MSN leaching was not observed from the PUs. The NO release payloads were also maintained for 4 days for polymers stored at 0 °C.

SUBMITTER: Malone-Povolny MJ

PROVIDER: S-EPMC6773253 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Extended Nitric Oxide-Releasing Polyurethanes via S-Nitrosothiol-Modified Mesoporous Silica Nanoparticles.

Malone-Povolny Maggie J MJ Schoenfisch Mark H MH

ACS applied materials & interfaces 20190319 13

S-Nitrosothiol (RSNO)-modified mesoporous silica nanoparticles (MSNs) were doped into polyurethane (PU) to achieve extended NO-releasing coatings. Parameters influencing the synthesis of RSNO-functionalized nitric oxide (NO)-releasing MSNs were evaluated to elucidate the impact of pore structure on NO release characteristics. The porous particles were characterized as having larger NO payloads and longer NO release durations than those of nonporous particles, a feature attributed to the recombin ...[more]

PMID: 30888145

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Project description:Purpose:Anticancer drug delivery systems are often limited by hurdles, such as off-target distribution, slow cellular internalization, limited lysosomal escape, and drug resistance. To overcome these limitations, we have developed a stable nitric oxide (NO)-releasing nanoparticle (polystyrene-maleic acid [SMA]-tert-dodecane S-nitrosothiol [tDodSNO]) with the aim of enhancing the anticancer properties of doxorubicin (Dox) and a Dox-loaded nanoparticle (SMA-Dox) carrier. Materials and methods:Effects of SMA-tDodSNO and/or in combination with Dox or SMA-Dox on cell viability, apoptosis, mitochondrial membrane potential, lysosomal membrane permeability, tumor tissue, and tumor growth were studied using in vitro and in vivo model of triple-negative breast cancer (TNBC). In addition, the concentrations of SMA-Dox and Dox in combination with SMA-tDodSNO were measured in cells and tumor tissues. Results:Combination of SMA-tDodSNO and Dox synergistically decreased cell viability and induced apoptosis in 4T1 (TNBC cells). Incubation of 4T1 cells with SMA-tDodSNO (40 µM) significantly enhanced the cellular uptake of SMA-Dox and increased Dox concentration in the cells resulting in a twofold increase (P<0.001). Lysosomal membrane integrity, evaluated by acridine orange (AO) staining, was impaired by 40 µM SMA-tDodSNO (P<0.05 vs control) and when combined with SMA-Dox, this effect was significantly potentiated (P<0.001 vs SMA-Dox). Subcutaneous administration of SMA-tDodSNO (1 mg/kg) to xenografted mice bearing 4T1 cells showed that SMA-tDodSNO alone caused a twofold decrease in the tumor size compared to the control group. SMA-tDodSNO in combination with SMA-Dox resulted in a statistically significant 4.7-fold reduction in the tumor volume (P<0.001 vs control), without causing significant toxicity as monitored through body weight loss. Conclusion:Taken together, these results suggest that SMA-tDodSNO can be used as a successful strategy to increase the efficacy of Dox and SMA-Dox in a model of TNBC.

Dataset Information

Extended Nitric Oxide-Releasing Polyurethanes via S-Nitrosothiol-Modified Mesoporous Silica Nanoparticles.

Publications

Extended Nitric Oxide-Releasing Polyurethanes via S-Nitrosothiol-Modified Mesoporous Silica Nanoparticles.

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