scholarly journals A Novel Mechanism Is Involved in Cationic Lipid-Mediated Functional siRNA Delivery

2009 ◽  
Vol 6 (3) ◽  
pp. 763-771 ◽  
Author(s):  
James J. Lu ◽  
Robert Langer ◽  
Jianzhu Chen
Keyword(s):  
Sirna Delivery ◽  
Cationic Lipid

scholarly journals Long-circulating siRNA nanoparticles for validating Prohibitin1-targeted non-small cell lung cancer treatment

2015 ◽  
Vol 112 (25) ◽  
pp. 7779-7784 ◽  
Author(s):  
Xi Zhu ◽  
Yingjie Xu ◽  
Luisa M. Solis ◽  
Wei Tao ◽  
Liangzhe Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Sirna Delivery ◽  
Cationic Lipid ◽  
Small Cell ◽  
Solid Polymer ◽  
Small Cell Lung ◽  
Formidable Challenge

RNA interference (RNAi) represents a promising strategy for identification and validation of putative therapeutic targets and for treatment of a myriad of important human diseases including cancer. However, the effective systemic in vivo delivery of small interfering RNA (siRNA) to tumors remains a formidable challenge. Using a robust self-assembly strategy, we develop a unique nanoparticle (NP) platform composed of a solid polymer/cationic lipid hybrid core and a lipid-poly(ethylene glycol) (lipid-PEG) shell for systemic siRNA delivery. The new generation lipid–polymer hybrid NPs are small and uniform, and can efficiently encapsulate siRNA and control its sustained release. They exhibit long blood circulation (t1/2 ∼8 h), high tumor accumulation, effective gene silencing, and negligible in vivo side effects. With this RNAi NP, we delineate and validate the therapeutic role of Prohibitin1 (PHB1), a target protein that has not been systemically evaluated in vivo due to the lack of specific and effective inhibitors, in treating non-small cell lung cancer (NSCLC) as evidenced by the drastic inhibition of tumor growth upon PHB1 silencing. Human tissue microarray analysis also reveals that high PHB1 tumor expression is associated with poorer overall survival in patients with NSCLC, further suggesting PHB1 as a therapeutic target. We expect this long-circulating RNAi NP platform to be of high interest for validating potential cancer targets in vivo and for the development of new cancer therapies.

scholarly journals Cationic lipid nanodisks as an siRNA delivery vehicle

2014 ◽  
Vol 92 (3) ◽  
pp. 200-205 ◽  
Author(s):  
Mistuni Ghosh ◽  
Gang Ren ◽  
Jens B. Simonsen ◽  
Robert O. Ryan
Keyword(s):  
Cell Model ◽  
Sirna Delivery ◽  
Aqueous Media ◽  
Density Lipoprotein ◽  
Cationic Lipid ◽  
Sucrose Density Gradient ◽  
Nucleic Acid Binding ◽  
Binding Studies ◽  
Bioactive Agents ◽  
Double Stranded Oligonucleotide

The term nanodisk (ND) describes reconstituted high-density lipoprotein particles that contain one or more exogenous bioactive agents. In the present study, ND were assembled from apolipoprotein A-I, the zwitterionic glycerophospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and the synthetic cationic lipid 1,2-dimyristoyl-3-trimethylammonium-propane (DMTAP). ND formulated at a DMPC:DMTAP ratio of 70:30 (by weight) were soluble in aqueous media. The particles generated were polydisperse, with diameters ranging from ∼20 to <50 nm. In nucleic acid binding studies, agarose gel retardation assays revealed that a synthetic 23-mer double-stranded oligonucleotide (dsOligo) bound to DMTAP containing ND but not to ND formulated with DMPC alone. Sucrose density gradient ultracentrifugation studies provided additional evidence for stable dsOligo binding to DMTAP–ND. Incubation of cultured hepatoma cells with DMTAP–ND complexed with a siRNA directed against glyceraldehyde 3-phosphate dehydrogenase showed 60% knockdown efficiency. Thus, incorporation of synthetic cationic lipid (i.e., DMTAP) to ND confers an ability to bind siRNA and the resulting complexes possess target gene knockdown activity in a cultured cell model.

Role of vitronectin-rich protein corona on tumor-specific siRNA delivery and transfection with lipid nanoparticles

Nanomedicine ◽  
2021 ◽  
Author(s):  
Dongyu Chen ◽  
Shanthi Ganesh ◽  
Weimin Wang ◽  
Adrien Lupieri ◽  
Mansoor Amiji
Keyword(s):  
Sirna Delivery ◽  
Cationic Lipid ◽  
Protein Corona ◽  
Lipid Nanoparticles ◽  
Αvβ3 Integrin ◽  
Systemic Delivery ◽  
Endothelial Lining ◽  
Endogenous Proteins

Aim: To evaluate the role of vitronectin-enriched protein corona on systemic delivery of siRNA-encapsulated cationic lipid nanoparticles (LNPs) to αvβ3 integrin expressing solid tumors. Materials & methods: 1,2-Dioleoyl-3-trimethylammonium-propane LNPs were formulated, protein corona formed in nude mice serum and its impact on drug delivery were analyzed. Results: 1,2-Dioleoyl-3-trimethylammonium-propane-containing LNP led to enhanced recruitment of vitronectin and showed preferential transfection to αvβ3-expressed cells relative to controls. Upon systemic administration in mice, the LNPs accumulated in the αvβ3-expressing endothelial lining of the tumor blood vessels before reaching tumor cells. Conclusion: These results present an optimized LNP that selectively recruits endogenous proteins in situ to its corona which may lead to enhanced delivery and transfection in tissues of interest.

scholarly journals Development of an Efficient Short Interference RNA (siRNA) Delivery System with a New pH-Sensitive Cationic Lipid

2012 ◽  
Vol 132 (12) ◽  
pp. 1355-1363 ◽  
Author(s):  
Yusuke Sato ◽  
Hiroto Hatakeyama ◽  
Mamoru Hyodo ◽  
Hidetaka Akita ◽  
Hideyoshi Harashima
Keyword(s):  
Delivery System ◽  
Sirna Delivery ◽  
Cationic Lipid ◽  
Ph Sensitive ◽  
Sirna Delivery System ◽  
Interference Rna

The development of tertiary amine cationic lipids for safe and efficient siRNA delivery

2019 ◽  
Vol 7 (7) ◽  
pp. 2777-2792 ◽  
Author(s):  
Ziming Lin ◽  
Moxyel Bao ◽  
Zexuan Yu ◽  
Lingjing Xue ◽  
Caoyun Ju ◽  
...  
Keyword(s):  
Tertiary Amine ◽  
Sirna Delivery ◽  
Cationic Lipid ◽  
Cationic Liposomes ◽  
Cationic Lipids

Tertiary amine-derived cationic lipid serves as the primary lipid of cationic liposomes, which can balance the effectiveness and safety of siRNA vectors.

Niosomes Containing Spermine-Based Cationic Lipid with Different Linkers for siRNA Delivery

2019 ◽  
Vol 819 ◽  
pp. 169-174
Author(s):  
Supusson Pengnam ◽  
Praneet Opanasopit ◽  
Theerasak Rojanarata ◽  
Nattisa Ni-yomtham ◽  
Boon Ek Yingyongnarongkul ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Cellular Uptake ◽  
Sirna Delivery ◽  
Weight Ratio ◽  
Cationic Lipid ◽  
Cationic Lipids ◽  
Molar Ratio ◽  
Ionic Surfactant ◽  
Low Toxicity ◽  
Cationic Niosomes

Niosomes are a lipid nanoparticle which have been widely used as non-viral carrier for therapeutic DNA or siRNA. They are formulated from non-ionic surfactant and other helper lipids. The aim of this study were to formulate niosome containing spermine-based cationic lipid with different linkers and to evaluate the efficiency of siRNA delivery in cervical cancer cell (HeLa cell). The niosomes were formulated from cholesterol (Chol), Span 20 and different cationic lipid (Ay, By, Cy and Dy) at various molar ratios. The properties of niosomes and ability of niosome to complex with siRNA were characterized. The cellular uptake, gene silencing efficiency and cytotoxicity were also determined. From the results, niosomes formulated at Chol:Span20:lipid molar ratio of 2.5:2.5:2 showed positive zeta potential and they were in nanosize (<200 nm). The binding ability of cationic niosomes to siRNA depended on types of cationic lipid. Among niosome/siRNA complexes, the niosome By/siRNA complex provided the highest gene silencing efficiency at weight ratio of 20. The highest cellular uptake also obtained by using niosome By as a carrier. The cytotoxicity revealed that cationic niosomes had low toxicity (cell viability > 80%). In conclusion, the cationic niosomes prepared from Chol, Span 20 and spermine-based cationic lipids are able to complex with siRNA and suitable for siRNA delivery with low toxicity.

siRNA Delivery Using a Cationic-Lipid-Based Highly Selective Human DNA Ligase I Inhibitor

2018 ◽  
Vol 10 (2) ◽  
pp. 1616-1622 ◽  
Author(s):  
Surendar R. Bathula ◽  
Komal Sharma ◽  
Deependra K. Singh ◽  
Muktapuram P. Reddy ◽  
Pushpa R. Sajja ◽  
...  
Keyword(s):  
Sirna Delivery ◽  
Cationic Lipid ◽  
Dna Ligase ◽  
Human Dna ◽  
Dna Ligase I

scholarly journals Anti-c-myc cholesterol based lipoplexes as onco-nanotherapeutic agents in vitro

F1000Research ◽  
2021 ◽  
Vol 9 ◽  
pp. 770
Author(s):  
Saffiya Habib ◽  
Aliscia Daniels ◽  
Mario Ariatti ◽  
Moganavelli Singh
Keyword(s):  
Sirna Delivery ◽  
Cationic Lipid ◽  
Lipid Vesicles ◽  
Breast Adenocarcinoma ◽  
Protein Levels ◽  
Anti Cancer ◽  
Attractive Option ◽  
Interfering Rna ◽  
Mcf 7

Background: Strategies aimed at inhibiting the expression of the c-myc oncogene could provide the basis for alternative cancer treatment. In this regard, silencing c-myc expression using small interfering RNA (siRNA) is an attractive option. However, the development of a clinically viable, siRNA-based, c-myc silencing system is largely dependent upon the design of an appropriate siRNA carrier that can be easily prepared. Nanostructures formed by the electrostatic association of siRNA and cationic lipid vesicles represent uncomplicated siRNA delivery systems. Methods: This study has focused on cationic liposomes prepared with equimolar quantities of the cytofectin, N,N-dimethylaminopropylamido-succinylcholesteryl-formylhydrazide (MS09), and cholesterol (Chol) for the development of a simple, but effective anti- c-myc onco-nanotherapeutic agent. Liposomes formulated with dioleoylphosphatidylethanolamine (DOPE) in place of Chol as the co-lipid were included for comparative purposes. Results: Liposomes successfully bound siRNA forming lipoplexes of less than 150 nm in size, which assumed bilamellar aggregrates. The liposome formulations were well tolerated in the human breast adenocarcinoma (MCF-7) and colon carcinoma (HT-29) cells, which overexpress c-myc. Lipoplexes directed against the c-myc transcript mediated a dramatic reduction in c-myc mRNA and protein levels. Moreover, oncogene knockdown and anti-cancer effects were superior to that of Lipofectamine™ 3000. Conclusion: This anti- c-myc MS09:Chol lipoplex exemplifies a simple anticancer agent with enhanced c-myc gene silencing potential in vitro

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