Combinational siRNA delivery using hyaluronic acid modified amphiphilic polyplexes against cell cycle and phosphatase proteins to inhibit growth and migration of triple-negative breast cancer cells

Parmar, Manoj B.; Sundaram, Daniel Nisakar Meenakshi; Bahadur, Krishna; Maranchuk, Robert A.; Aliabadi, Hamidreza Montazeri; Hugh, Judith; Löbenberg, Raimar; Uludağ, Hasan

doi:10.1016/j.actbio.2017.11.036

Cited by 30 publications

(24 citation statements)

References 57 publications

(67 reference statements)

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“…Some properties of siRNA/polycation/hyaluronic acid nanocarriers formed by electrostatic interactions are influenced by the component mixing order during their preparation [141,154]. siRNA protection, cellular uptake, and gene silencing were found to be better when siRNA was initially mixed with hyaluronic acid or hyperbranched poly(amido amine) (PCD) and then added to the oppositely charged polymer, than when HA/PCD binary complexes were prepared and subsequently incubated with siRNA.…”

Section: Hyaluronic Acid For Sirna Deliverymentioning

confidence: 99%

Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives

et al. 2019

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Natural polysaccharides are frequently used in the design of drug delivery systems due to their biocompatibility, biodegradability, and low toxicity. Moreover, they are diverse in structure, size, and charge, and their chemical functional groups can be easily modified to match the needs of the final application and mode of administration. This review focuses on polysaccharidic nanocarriers based on chitosan and hyaluronic acid for small interfering RNA (siRNA) delivery, which are highly positively and negatively charged, respectively. The key properties, strengths, and drawbacks of each polysaccharide are discussed. In addition, their use as efficient nanodelivery systems for gene silencing applications is put into context using the most recent examples from the literature. The latest advances in this field illustrate effectively how chitosan and hyaluronic acid can be modified or associated with other molecules in order to overcome their limitations to produce optimized siRNA delivery systems with promising in vitro and in vivo results.

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Section: Hyaluronic Acid For Sirna Deliverymentioning

confidence: 99%

Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives

et al. 2019

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“…Hyaluronic acid (HA), a negatively charged polysaccharide, is present in the extracellular matrix and synovial fluids (Knopf-Marques et al, 2016). It can cover on the shell of positive nano-carriers, such as PEI-PE, chitosan, dendrimer, to decrease the uptake rate by reticuloendothelial systems (Nguyen and Alsberg, 2014; Zhao et al, 2016; Wickens et al, 2017; Parmar et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Liver-Targeted Combination Therapy Basing on Glycyrrhizic Acid-Modified DSPE-PEG-PEI Nanoparticles for Co-delivery of Doxorubicin and Bcl-2 siRNA

et al. 2019

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Combination therapy based on nano-sized drug delivery system has been developed as a promising strategy by combining two or more anti-tumor mechanisms. Here, we prepared liver-targeted nanoparticles (GH-DPP) composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-polyetherimide (DSPE-PEG-PEI) with Glycyrrhetinic acid-modified hyaluronic acid (GA-HA) for co-delivery of doxorubicin (DOX) and Bcl-2 siRNA. Particles size, zeta potential and morphology were determined for the drug-loaded GH-DPP nanoparticles (siRNA/DOX/GH-DPP). Cellular uptake and in vitro cytotoxicity were analyzed against HepG2 cells. In vivo bio-distribution and anti-tumor therapeutic effects of siRNA/DOX/GH-DPP were evaluated in H22-bearing mice. The results showed that siRNA/DOX/GH-DPP nanoparticles were nearly spherical and showed dose-dependent cytotoxicity against HepG2 cells. Compared to Glycyrrhetinic acid-free co-delivery system (siRNA/DOX/DPP) and GH-DPP nanoparticles for delivery of DOX or Bcl-2 siRNA alone, siRNA/DOX/GH-DPP nanoparticles could induce more cellular apoptosis, and showed higher anti-tumor effect. Herein GH-DPP nanoparticles could simultaneously deliver both chemotherapy drugs and siRNA into the tumor region, exhibiting great potential in anti-tumor therapy.

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“…For example, Alexander et al optimized PEI-based nanoparticles for siRNA delivery, then analyzed the results in in vitro and in vivo tumor tissue slice culture models [29]. Parmar et al formulated an siRNA delivery system using lipid-substituted PEI and hyaluronic acid to inhibit growth and migration of triple-negative breast cancer cells [30]. To deliver siRNA into macrophages and B cells for BTK gene silencing, Zhao et al employed a cationic lipid-assisted PEG-b-PLGA nanoparticle (CLAN) to encapsulate siRNA [31].…”

Section: Discussionmentioning

confidence: 99%

Efficient Treatment of Rheumatoid Arthritis by Degradable LPCE Nano-Conjugate-Delivered p65 siRNA

et al. 2022

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Rheumatoid arthritis (RA) is one of the most common autoimmune diseases worldwide, causing severe cartilage damage and disability. Despite the recent progress made in RA treatment, limitations remain in achieving early and efficient therapeutic intervention. Advanced therapeutic strategies are in high demand, and siRNA-based therapeutic technology with a gene-silencing ability represents a new approach for RA treatment. In this study, we created a cationic delivery micelle consisting of low-molecular-weight (LMW) polyethylenimine (PEI)–cholesterol–polyethylene glycol (PEG) (LPCE) for small interfering RNA (siRNA)-based RA gene therapy. The carrier is based on LMW PEI and modified with cholesterol and PEG. With these two modifications, the LPCE micelle becomes multifunctional, and it efficiently delivered siRNA to macrophages with a high efficiency greater than 70%. The synthesized LPCE exhibits strong siRNA protection ability and high safety. By delivering nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 siRNA, the p65 siRNA/LPCE complex efficiently inhibited macrophage-based cytokine release in vitro. Local administration of the p65 siRNA/LPCE complex exhibited a fast and potent anti-inflammatory effect against RA in a mouse model. According to the results of this study, the functionalized LPCE micelle that we prepared has potential gene therapeutic implications for RA.

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Combinational siRNA delivery using hyaluronic acid modified amphiphilic polyplexes against cell cycle and phosphatase proteins to inhibit growth and migration of triple-negative breast cancer cells

Cited by 30 publications

References 57 publications

Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives

Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives

Liver-Targeted Combination Therapy Basing on Glycyrrhizic Acid-Modified DSPE-PEG-PEI Nanoparticles for Co-delivery of Doxorubicin and Bcl-2 siRNA

Efficient Treatment of Rheumatoid Arthritis by Degradable LPCE Nano-Conjugate-Delivered p65 siRNA

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