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Influence of scaffold size on bactericidal activity of nitric oxide-releasing silica nanoparticles.

ABSTRACT: A reverse microemulsion synthesis was used to prepare amine-functionalized silica nanoparticles of three distinct sizes (i.e., 50, 100, and 200 nm) with similar amine content. The resulting hybrid nanoparticles, consisting of N-(6-aminohexyl)aminopropyltrimethoxysilane and tetraethoxysilane, were highly monodisperse in size. N-Diazeniumdiolate nitric oxide (NO) donors were subsequently formed on secondary amines while controlling reaction conditions to keep the total amount of NO released constant for each particle size. The bactericidal efficacy of the NO-releasing nanoparticles against Pseudomonas aeruginosa increased with decreasing particle size. Additionally, smaller diameter nanoparticles were found to associate with the bacteria at a faster rate and to a greater extent than larger particles. Neither control (non-NO-releasing) nor NO-releasing particles exhibited toxicity toward L929 mouse fibroblasts at concentrations above their respective minimum bactericidal concentrations. This study represents the first investigation of the bactericidal efficacy of NO-releasing silica nanoparticles as a function of particle size.

SUBMITTER: Carpenter AW

PROVIDER: S-EPMC3225065 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Influence of scaffold size on bactericidal activity of nitric oxide-releasing silica nanoparticles.

Carpenter Alexis W AW Slomberg Danielle L DL Rao Kavitha S KS Schoenfisch Mark H MH

ACS nano 20110829 9

A reverse microemulsion synthesis was used to prepare amine-functionalized silica nanoparticles of three distinct sizes (i.e., 50, 100, and 200 nm) with similar amine content. The resulting hybrid nanoparticles, consisting of N-(6-aminohexyl)aminopropyltrimethoxysilane and tetraethoxysilane, were highly monodisperse in size. N-Diazeniumdiolate nitric oxide (NO) donors were subsequently formed on secondary amines while controlling reaction conditions to keep the total amount of NO released consta ...[more]

PMID: 21842899

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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

Influence of scaffold size on bactericidal activity of nitric oxide-releasing silica nanoparticles.

Publications

Influence of scaffold size on bactericidal activity of nitric oxide-releasing silica nanoparticles.

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