Glutathione targeted tragacanthic acid-chitosan as a non-viral vector for brain delivery of miRNA-219a-5P: An in vitro/in vivo study

Shamaeizadeh, Nahal; Varshosaz, Jaleh; Mirian, Mina; Aliomrani, Mehdi

doi:10.1016/j.ijbiomac.2022.01.100

Cited by 19 publications

(10 citation statements)

References 69 publications

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“…Apos can act as intrinsic docking and plasma membrane entry facilitators and are exploited by hepatitis C to enable virus entry 13 – 16 . Apos have recently been used to create thermostable lipid-like nanoparticles for delivery of RNAi 17 , miRNA 18 , siRNA 19 , and small molecule therapies 20 . These studies demonstrate that targeting of specific tissues appears to be dependent upon the type of Apo or combination of Apos that were used to coat the nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein C3 facilitates internalization of cationic lipid nanoparticles into bone marrow-derived mouse mast cells

Alam

Wang

Qian

et al. 2023

Sci Rep

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Mast cells (MCs), are hematopoetically-derived secretory immune cells that release preformed as well as de novo synthesized inflammatory mediators in response to activation by several stimuli. Based on their role in inflammatory responses, particularly in the lung and skin, MCs provide an effective target for anti-inflammatory therapeutic strategies. Drug-delivery of lipophilic payloads to MCs can be challenging due to their functionally distinct intracellular structures. In the present study, pH-sensitive cationic lipid-based nanoparticles (LNPs) composed of DODMA, DODAP or DOTAP lipids that encapsulated a GFP or eGFP plasmid were constructed using non-turbulent microfluidic mixing. This approach achieved up to 75–92% encapsulation efficiency. Dynamic light scattering revealed a uniformly sized and homogeneous dispersion of LNPs. To promote cellular internalization, LNPs were complexed with apolipoproteins, amphipathic proteins capable of binding lipids and facilitating their transport into cells. Cryo-TEM analysis showed that LNP structure was differentially modified when associated with different types of apolipoproteins. LNP preparations made up of DODMA or DODMA, DODAP and DOTAP lipids were coated with seven apolipoproteins (Apo A1, B, C3, D, E2, E4 and H). Differentiated bone-marrow derived mouse mast cells (BMMCs) were exposed to apolipoprotein-LNP and internalization was measured using flow cytometry. Out of all the apolipoproteins tested, ApoC3 most efficiently facilitated cellular internalization of the LNP into BMMCs as determined by GFP fluorescence using flow cytometry. These effects were confirmed in a less differentiated but also interleukin-3-dependent model of mouse mast cells, MC/9. ApoC3-LNP enhanced internalization by BMMC in a concentration-dependent manner and this was significantly increased when BMMC were pre-treated with inhibitors of actin polymerization, suggesting a dependence on intracellular shuttling. Activation of peroxisome proliferator-activated receptor gamma (PPARγ) decreased ApoC3-LNP internalization and reduced the expression of apolipoprotein E receptor 2 (ApoER2), suggesting that ApoC3-LNP binding to ApoER2 may be responsible for its enhanced internalization. Furthermore, ApoC3 fails to facilitate internalization of LNPs in Lrp8−/− KO BMMC that do not express ApoER2 on their cell surface. Altogether, our studies reveal an important role of ApoC3 in facilitating internalization of cationic LNPs into MCs.

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Section: Introductionmentioning

confidence: 99%

Apolipoprotein C3 facilitates internalization of cationic lipid nanoparticles into bone marrow-derived mouse mast cells

Alam

Wang

Qian

et al. 2023

Sci Rep

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“…We found that our CNPs were similar to those in Denizli et al (2017) [14] and K. Kaban et al (2017) [17], which used the same chitosan type and N/P ratio. Our CNPs were smaller and more positively charged than those in Shamaeizadeh et al (2022) [12] and Deng et al (2014) [15], which used chitosan with higher acetylation and molecular weight, and added other components. Our CNPs were comparable to those in Santos-Carballal et al (2015) [24], which used different chitosan types but the same N/P ratio.…”

Section: Discussion Of Cnps Characteristicsmentioning

confidence: 70%

“…However, we found some papers that used chitosan-based carriers for delivery of other miRNAs to other types of cancer cells. For example, Shamaeizadeh et al ( 2022) used glutathione targeted tragacanthic acid-chitosan nanoparticles to deliver miRNA-219a-5P to glioma cells and found that they enhanced the cellular uptake, the expression, and the neuroprotective effect of miRNA-219a-5P [12]. Su et al ( 2020) used chitosan hydrogel doped with PEG-PLA nanoparticles to deliver miRNA-146a to the nasal mucosa of rats with allergic rhinitis and found that they improved the stability, the permeability, and the anti-in ammatory effect of miRNA-146a [11].…”

Section: Discussion Of Cnps Release Pro Lementioning

confidence: 99%

Synthesis and evaluation of chitosan/miR-125b nanoparticles for targeting Raf-1 and BMPR1b genes in MCF-7 breast cancer cells

Norouzi,

Abousalehi,

Afshar

2024

Preprint

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MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play important roles in cancer development and progression. MiR-125b-5p is a miRNA that has been reported to have diverse and context-dependent effects on different cancer types and subtypes. In this study, we aimed to investigate the expression and function of miR-125b-5p in MCF-7 breast cancer cells and to explore the potential of using chitosan nanoparticles for miR-125b-5p delivery. We found that miR-125b-5p was downregulated in MCF-7 cells compared to normal mammary epithelial cells, and that its overexpression reduced the viability of MCF-7 cells by targeting Raf-1 and BMPR1b genes, which are involved in cell survival and proliferation. We also synthesized and characterized chitosan/miR-125b nanoparticles (CNPs) and evaluated their in vitro release profile and cellular uptake. We showed that CNPs enhanced the delivery and efficiency of miR-125b-5p, resulting in a more potent inhibition of Raf-1 and BMPR1b gene expression and a greater reduction of cell viability. Our results suggest that miR-125b-5p and CNPs have potential anti-tumor effects on human breast cancer cells by suppressing Raf-1 and BMPR1b gene expression. Our study provides a new insight into the role and mechanism of miR-125b-5p and its target genes in breast cancer, and demonstrates the feasibility and efficacy of using chitosan nanoparticles for miR-125b-5p delivery.

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“…The cuprizone model of MS mice, upon injecting the polyplex NPs, showed proteolipid protein 1 (Plp1) overexpression leads to reduced inflammation, apolipoprotein E downregulation, crystallin alpha B upregulation, and improved myelin sheaths in the brain. Therefore, glutathione-targeted Ch/TA nanoparticles could be exploited as a feasible nonviral vector for miRNA-219-specific targeting to the brain for inflammatory abatement in MS. 210 The regeneration of myelin (called remyelination) is the key strategy to combat MS in the brain. To promote remyelination via miRNAs, Osorio-Querejeta and colleagues, investigated miRNA-219a-5p embedded Distearoylphosphatidylcholine (DSPC) liposome and poly-lactic-co-glycolic acid (PLGA) nanoparticles in C57BL/6 female MS mice.…”

Section: Mirna Based Targeted Therapeutics In Adsmentioning

confidence: 99%

Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review

Nag,

Mitra,

Tripathi

et al. 2023

Immunity Inflam & Disease

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BackgroundAutoimmune diseases (AD) are severe pathophysiological ailments that are stimulated by an exaggerated immunogenic response towards self‐antigens, which can cause systemic or site‐specific organ damage. An array of complex genetic and epigenetic facets majorly contributes to the progression of AD, thus providing significant insight into the regulatory mechanism of microRNA (miRNA). miRNAs are short, non‐coding RNAs that have been identified as essential contributors to the post‐transcriptional regulation of host genome expression and as crucial regulators of a myriad of biological processes such as immune homeostasis, T helper cell differentiation, central and peripheral tolerance, and immune cell development.AimsThis article tends to deliberate and conceptualize the brief pathogenesis and pertinent epigenetic regulatory mechanism as well as miRNA networks majorly affecting five different ADs namely rheumatoid arthritis (RA), type 1 diabetes, multiple sclerosis (MS), systemic lupus erythematosus (SLE) and inflammatory bowel disorder (IBD) thereby providing novel miRNA‐based theranostic interventions.Results & DiscussionPertaining to the differential expression of miRNA attributed in target tissues and cellular bodies of innate and adaptive immunity, a paradigm of scientific expeditions suggests an optimistic correlation between immunogenic dysfunction and miRNA alterations.ConclusionTherefore, it is not astonishing that dysregulations in miRNA expression patterns are now recognized in a wide spectrum of disorders, establishing themselves as potential biomarkers and therapeutic targets. Owing to its theranostic potencies, miRNA targets have been widely utilized in the development of biosensors and other therapeutic molecules originating from the same.

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Glutathione targeted tragacanthic acid-chitosan as a non-viral vector for brain delivery of miRNA-219a-5P: An in vitro/in vivo study

Cited by 19 publications

References 69 publications

Apolipoprotein C3 facilitates internalization of cationic lipid nanoparticles into bone marrow-derived mouse mast cells

Apolipoprotein C3 facilitates internalization of cationic lipid nanoparticles into bone marrow-derived mouse mast cells

Synthesis and evaluation of chitosan/miR-125b nanoparticles for targeting Raf-1 and BMPR1b genes in MCF-7 breast cancer cells

Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review

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