Sterically Stabilized siRNA:Gold Nanocomplexes Enhance
            <i>c-MYC</i>
            Silencing in a Breast Cancer Cell Model

Daniels, Aliscia; Singh, Moganavelli

doi:10.2217/nnm-2018-0462

Cited by 43 publications

(30 citation statements)

References 36 publications

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“…The degree of FA substitution as determined by UV spectroscopy was 1.9%, which we attribute to the high molecular weight of chitosan, which has been reported to decrease FA substitution [32]. Degrees of substitution of 0.58-2.2% have been used successfully in gene and drug delivery [27,33,34]. The particle size of SeChFA increased (75.6 ± 1.4 nm), with a corresponding reduction in ζ potential (9.0 ± 0.3 mV), which could be attributed to substitution of amino groups with FA, as well as the possible shielding of the positive charges by FA.…”

Section: Preparation and Characterization Of Nanoparticlesmentioning

confidence: 85%

“…Chitosan, a positively charged natural polysaccharide made up of β (1-4)-glucosamine and N-acetyl-D-glucosamine is one of the most attractive polymers for gene delivery, owing to its cationic nature, low cytotoxicity, low immunogenicity, and biocompatibility. It has been successfully used in the delivery of pDNA and siRNA [24][25][26][27]. Herein, we evaluate the transfection efficiency of Fluc-mRNA conjugated to chitosan-coated SeNPs, a biodegradable core-shell carrier with a folate targeting moiety, as a potential nanodelivery vehicle to cancer cells in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Folate-Targeted mRNA Delivery Using Chitosan-Functionalized Selenium Nanoparticles: Potential in Cancer Immunotherapy

Maiyo

Singh

2019

Pharmaceuticals

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Systemic messenger RNA (mRNA) delivery, although still in its infancy, holds immense potential for application in cancer vaccination and immunotherapy. Its advantages over DNA transfection make it attractive in applications where transient expression is desired. However, this has proved challenging due to mRNA’s instability and susceptibility to degradation. Selenium is important for immune function and modulation, with selenium nanoparticles (SeNPs) finding a niche in biomedicine as drug delivery vehicles, owing to their biocompatibility, low toxicity, and biodegradability. In this investigation, we synthesized chitosan-coated SeNPs with a folic acid targeting moiety for Fluc mRNA delivery to cancer cells in vitro. Synthesized SeNPs were stable and well dispersed, and ranged from 59 to 102 nm in size. Nanoparticles bound and protected mRNA from RNase degradation, while exhibiting low cytotoxicity in the human embryonic kidney (HEK293), breast adenocarcinoma (MCF-7), and nasopharyngeal (KB) cells in culture. Moderate cytotoxicity evidenced in the colorectal carcinoma (Caco-2) and colon carcinoma (HT-29) cells was attributed to apoptosis induction by selenium, as confirmed by acridine orange/ethidium bromide staining. Selenium uptake studies corroborated the transfection results, where significant transgene expression was evident for the overexpressed folate receptor-positive KB cells when compared to the other cells with less or no folate receptors.

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Section: Preparation and Characterization Of Nanoparticlesmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Folate-Targeted mRNA Delivery Using Chitosan-Functionalized Selenium Nanoparticles: Potential in Cancer Immunotherapy

Maiyo

Singh

2019

Pharmaceuticals

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“…The use of a chitosan shell and selenium core was previously utilized for the delivery of FLuc-mRNA and showed significant transgene expression and low cytotoxicity in vitro [28]. The choice of this particular molecular weight of chitosan used was based on studies conducted earlier in out laboratory [28,[42][43][44][45]. This inorganic SeNP core and a cationic chitosan shell were further modified with a targeting folic acid moiety for cancer cell-specific delivery.…”

Section: Discussionmentioning

confidence: 99%

“…This inorganic SeNP core and a cationic chitosan shell were further modified with a targeting folic acid moiety for cancer cell-specific delivery. Chitosan has previously been used to alter the stability and morphology of inorganic nanoparticles in numerous studies due to its suitability in biomedical applications owing to its non-immunogenicity and biodegradability in vivo [16,[44][45][46][47]. Furthermore, it promotes nanoparticle retention in the cell, thus improving its bioactivity.…”

Section: Discussionmentioning

confidence: 99%

Polymerized Selenium Nanoparticles for Folate-Receptor-Targeted Delivery of Anti-Luc-siRNA: Potential for Gene Silencing

Maiyo

Singh

2020

Biomedicines

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The development of a biocompatible and nontoxic gene delivery vehicle remains a challenging task. Selenium nanoparticles (SeNPs) have the potential to increase delivery efficiency, to reduce side effects, and to improve therapeutic outcomes. In this study, chitosan (Ch) functionalized folate (FA)-targeted SeNPs were synthesized, characterized, and evaluated for their potential to bind, protect, and safely deliver Fluc-siRNA in vitro. SeNPs of less than 100 nm were successfully synthesised and further confirmed using UV-vis and Fourier transform infrared spectroscopy, transmission electron microscopy, and nanoparticle tracking analysis. Cell viability studies were conducted in vitro in selected cancer and non-cancer cell lines. Folate receptor (FOLR1) targeted and nontargeted luciferase gene silencing studies were assessed in the transformed Hela-tat-Luc cell line expressing the luciferase gene. Targeted and nontargeted SeNP nanocomplexes showed minimal toxicity in all cell lines at selected w/w ratios. Maximum gene silencing was achieved at optimum w/w ratios for both nanocomplexes, with Selenium-chitosan-folic acid (SeChFA) nanocomplexes showing slightly better transgene silencing, as supported by results from docking studies showing that SeChFA nanocomplexes interacted strongly with the folate receptor (FOLR1) with high binding energy of −4.4 kcal mol−1.

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“…A method described by Daniels and Singh [ 24 ] was adopted to evaluate cytotoxicity of the bioflocculant and nanoparticles using human embryonic kidney (HEK 293) and breast cancer cells (MCF-7). Cells with cell suspensions of 1 × 10 5 cells/mL concentrations were platted on 96-well-plate.…”

Section: Methodsmentioning

confidence: 99%

Wastewater Treatment by a Polymeric Bioflocculant and Iron Nanoparticles Synthesized from a Bioflocculant

2020

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Wastewater remains a global challenge. Various methods have been used in wastewater treatment, including flocculation. The aim of this study was to synthesize iron nanoparticles (FeNPs) using a polymeric bioflocculant and to evaluate its efficacy in the removal of pollutants in wastewater. A comparison between the efficiencies of the bioflocculant and iron nanoparticles was investigated. A scanning electron microscope (SEM) equipped with an energy-dispersive X-ray analyzer (EDX) and Fourier transform-infrared (FT-IR) spectroscopy were used to characterize the material. SEM-EDX analysis revealed the presence of elements such as O and C that were abundant in both samples, while FT-IR studies showed the presence of functional groups such as hydroxyl (–OH) and amine (–NH2). Fe nanoparticles showed the best flocculation activity (FA) at 0.4 mg/mL dosage as opposed to that of the bioflocculant, which displayed the highest flocculation activity at 0.8 mg/mL, and both samples were found to be cation-dependent. When evaluated for heat stability and pH stability, FeNPs were found thermostable with 86% FA at 100 °C, while an alkaline pH of 11 favored FA with 93%. The bioflocculant flocculated poorly at high temperature and was found effective mostly at a pH of 7 with over 90% FA. FeNPs effectively removed BOD (biochemical oxygen demand) and COD (chemical oxygen demand) in all two wastewater samples from coal mine water and Mzingazi River water. Cytotoxicity results showed both FeNPs and the bioflocculant as nontoxic at concentrations up to 50 µL.

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Sterically Stabilized siRNA:Gold Nanocomplexes Enhance c-MYC Silencing in a Breast Cancer Cell Model

Cited by 43 publications

References 36 publications

Folate-Targeted mRNA Delivery Using Chitosan-Functionalized Selenium Nanoparticles: Potential in Cancer Immunotherapy

Folate-Targeted mRNA Delivery Using Chitosan-Functionalized Selenium Nanoparticles: Potential in Cancer Immunotherapy

Polymerized Selenium Nanoparticles for Folate-Receptor-Targeted Delivery of Anti-Luc-siRNA: Potential for Gene Silencing

Wastewater Treatment by a Polymeric Bioflocculant and Iron Nanoparticles Synthesized from a Bioflocculant

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