siRNA delivery with chitosan nanoparticles: Molecular properties favoring efficient gene silencing

Malmo, Jostein; Sørgård, Hanne; Vårum, Kjell M.; Strand, Sabina P.

doi:10.1016/j.jconrel.2011.11.012

Cited by 113 publications

(123 citation statements)

References 38 publications

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“…Chitosan is a cationic polysaccharide first introduced to gene delivery in the late 1990s [83] that can be adapted to different nucleic acid cargoes by modifying the chain architecture and/or the acetylation and polymerization degree. [84] Thus, while 80% deacetylated chitosan showed low efficiencies transfecting pDNA, fully deacetylated chitosan demonstrated remarkable functionality of the eluted siRNA along a 5 d time-course in a human lung carcinoma cell line (H1299). [84] More recently, shortening the chain length has provided improved efficiencies (≈45%) in the transfection of rat mesenchymal stem cells with pDNA, [85] and similarly, highly depolymerized chitosan delivering miR-145 to human breast adenocarcinoma (MCF-7) cells achieved ≈50% target silencing.…”

Section: Nonviral Vectorsmentioning

confidence: 95%

“…[84] Thus, while 80% deacetylated chitosan showed low efficiencies transfecting pDNA, fully deacetylated chitosan demonstrated remarkable functionality of the eluted siRNA along a 5 d time-course in a human lung carcinoma cell line (H1299). [84] More recently, shortening the chain length has provided improved efficiencies (≈45%) in the transfection of rat mesenchymal stem cells with pDNA, [85] and similarly, highly depolymerized chitosan delivering miR-145 to human breast adenocarcinoma (MCF-7) cells achieved ≈50% target silencing. [86] Exosomes play a critical role in paracrine signaling and intercellular miRNA trafficking guided by the tissue-specific proteins found on their surface.…”

Section: Nonviral Vectorsmentioning

confidence: 95%

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Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Curtin

Castaño

O’Brien

2017

Adv Healthcare Materials

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The field of "regenerative medicine" (RM) was conceptually developed to aid the body's natural capacity to self-repair, a capacity which is impaired with age and in cases of disease or injury. [1] RM is a vast and multifaceted area of medicine, often microRNA-based therapies are an advantageous strategy with applications in both regenerative medicine (RM) and cancer treatments. microRNAs (miRNAs) are an evolutionary conserved class of small RNA molecules that modulate up to one third of the human nonprotein coding genome. Thus, synthetic miRNA activators and inhibitors hold immense potential to finely balance gene expression and reestablish tissue health. Ongoing industrysponsored clinical trials inspire a new miRNA therapeutics era, but progress largely relies on the development of safe and efficient delivery systems. The emerging application of biomaterial scaffolds for this purpose offers spatiotemporal control and circumvents biological and mechanical barriers that impede successful miRNA delivery. The nascent research in scaffold-mediated miRNA therapies translates know-how learnt from studies in antitumoral and genetic disorders as well as work on plasmid (p)DNA/siRNA delivery to expand the miRNA therapies arena. In this progress report, the state of the art methods of regulating miRNAs are reviewed. Relevant miRNA delivery vectors and scaffold systems applied to-date for RM and cancer treatment applications are discussed, as well as the challenges involved in their design. Overall, this progress report demonstrates the opportunity that exists for the application of miRNA-activated scaffolds in the future of RM and cancer treatments.Regenerative Medicine

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Section: Nonviral Vectorsmentioning

confidence: 95%

Section: Nonviral Vectorsmentioning

confidence: 95%

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Curtin

Castaño

O’Brien

2017

Adv Healthcare Materials

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“…CH-DEAE 15 /siRNA and folate-PEG-CH-DEAE 15 / siRNA complexes were processed at amino groups/phosphate groups (N/P) ratio of 2:1 by a coacervation method, with the equivalent of 50 µg siRNA in each preparation, as previously described. [33][34][35] Particle size and zeta potential were measured by Zetasizer Nano ZS90 (Malvern Instruments Ltd., Malvern, UK).…”

Section: Nanoparticle Preparation and Characterizationmentioning

confidence: 99%

In vivo therapeutic efficacy of TNFα silencing by folate-PEG-chitosan-DEAE/siRNA nanoparticles in arthritic mice

Shi¹,

Rondon-Cavanzo²,

Picola³

et al. 2018

IJN

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Background Tumor necrosis factor-alpha (TNFα), a pro-inflammatory cytokine, has been shown to play a role in the pathophysiology of rheumatoid arthritis. Silencing TNFα expression with small interfering RNA (siRNA) is a promising approach to treatment of the condition. Methods Towards this end, our team has developed a modified chitosan (CH) nanocarrier, deploying folic acid, diethylethylamine (DEAE) and polyethylene glycol (PEG) (folate-PEG-CH-DEAE 15 ). The gene carrier protects siRNA against nuclease destruction, its ligands facilitate siRNA uptake via cell surface receptors, and it provides improved solubility at neutral pH with transport of its load into target cells. In the present study, nanoparticles were prepared with siRNA-TNFα, DEAE, and folic acid-CH derivative. Nanoparticle size and zeta potential were verified by dynamic light scattering. Their TNFα-knockdown effects were tested in a murine collagen antibody-induced arthritis model. TNFα expression was examined along with measurements of various cartilage and bone turnover markers by performing histology and microcomputed tomography analysis. Results We demonstrated that folate-PEG-CH-DEAE 15 /siRNA nanoparticles did not alter cell viability, and significantly decreased inflammation, as demonstrated by improved clinical scores and lower TNFα protein concentrations in target tissues. This siRNA nanocarrier also decreased articular cartilage destruction and bone loss. Conclusion The results indicate that folate-PEG-CH-DEAE 15 nanoparticles are a safe and effective platform for nonviral gene delivery of siRNA, and their potential clinical applications warrant further investigation.

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“…The positive charge of chitosan allows for fixing the negatively charged siRNAs to the vector surface by electrostatic attraction. Chitosan was selected as the transacylation polymer for its interesting physicochemical properties in particular its non-toxicity and biocompatibility (30).…”

Section: Introductionmentioning

confidence: 99%

Combined silencing expression of MGMT with EGFR or galectin-1 enhances the sensitivity of glioblastoma to temozolomide

Messaoudi

Clavreul

Danhier

et al. 2015

European Journal of Nanomedicine

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For several years, the first line of treatment of glioblastoma (GB) patients is based on surgical resection followed by fractioned radiotherapy with concomitant and adjuvant chemotherapy with temozolomide (TMZ). The effectiveness of this treatment is very limited due to the development by tumor cells of mechanisms of resistance to TMZ such as over-expression of O6-methylguanine DNA methyltransferase (MGMT), epidermal growth factor receptor (EGFR) and galectin-1. In this study, we hypothesized that the targeting of MGMT, EGFR and galectin-1 (alone or in combination) by specifics siRNAs carried by chitosan-lipid nanocapsules (chitosan-LNCs) could enhance the sensitivity of U87MG cells to TMZ. We showed in vitro that (i) anti-MGMT and (ii) anti-EGFR or anti-galectin-1 siRNAs decreased significantly the expression of their corresponding proteins and increased the sensitivity of U87MG cells to TMZ. Additionally, the sensitivity of U87MG/MGMT-cells to TMZ was significantly increased when anti-EGFR and anti-galectin-1 siRNAs were combined with a percentage of living cells of 17.8±1.6% at 0.5 mg/mL concentration of TMZ. The combination of anti-MGMT siRNAs with either anti-EGFR or anti-galectin-1 siRNAs enhanced the sensitivity of U87MG/ MGMT+ cells to TMZ in comparison to their separately use. No difference was observed between the association of the three siRNAs and other associations. At 0.5 mg/ mL concentration of TMZ, the percentage of living cells decreased from 55.1±1.9% to 36.0±4.1% for anti-MGMT alone and the combination of anti-MGMT/anti-galectin-1/ anti-EGFR siRNAs, respectively. These siRNA nanovectors represent a good alternative to enhance the effectiveness of the standard treatment of GB. This method could be implemented in future preclinical models for experimental cancer treatment of GB.

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siRNA delivery with chitosan nanoparticles: Molecular properties favoring efficient gene silencing

Cited by 113 publications

References 38 publications

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

In vivo therapeutic efficacy of TNFα silencing by folate-PEG-chitosan-DEAE/siRNA nanoparticles in arthritic mice

Combined silencing expression of MGMT with EGFR or galectin-1 enhances the sensitivity of glioblastoma to temozolomide

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siRNA delivery with chitosan nanoparticles: Molecular properties favoring efficient gene silencing

Cited by 113 publications

References 38 publications

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

In vivo therapeutic efficacy of TNF&alpha; silencing by folate-PEG-chitosan-DEAE/siRNA nanoparticles in arthritic mice

Combined silencing expression of MGMT with EGFR or galectin-1 enhances the sensitivity of glioblastoma to temozolomide

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In vivo therapeutic efficacy of TNFα silencing by folate-PEG-chitosan-DEAE/siRNA nanoparticles in arthritic mice