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

Abstract

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 200 nm in size, which assumed globular, bilamellar structures. 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.

Hepatocellular-Targeted mRNA Delivery Using Functionalized Selenium Nanoparticles In Vitro

“…It was reported that internalization of negatively charged NPs is mediated through independent and dependent caveolin and/or clathrin-mediated endocytosis. Internalization of NPs through these pathways is size-dependent, with a size range of 120–150 nm required for internalization and a maximum size of 200 nm being reported for internalization [ 79 ]. Although it is accepted that a net positive charge allows for binding to anionic membrane-associated proteoglycans to initiate cellular uptake, it is also possible for mRNA nanocomplexes with a negative zeta potential to enter cells and successfully facilitate gene expression, as we have shown with similar results being reported using siRNA lipoplexes [ 80 ].…”

Dendrimer-Coated Gold Nanoparticles for Efficient Folate-Targeted mRNA Delivery In Vitro

“…The use of the RNase enzyme was a stringent test for these NPs due to its specificity for RNA molecules and was reported previously [ 53 , 54 ]. Various studies have used the less-specific fetal bovine serum containing nucleases to determine the integrity of RNA-based nanocomplexes [ 55 , 56 ] to achieve similar results. In the circulatory system, it is possible that the nanoparticles may encounter less-specific enzymes and possibly at lower concentrations as well.…”

Nanomedicine for Neurodegenerative Disorders: Focus on Alzheimer’s and Parkinson’s Diseases

“…Due to inorganic NPs portraying greater surface area to volume ratios with tunable magnetic, optical, and biological properties, they can be engineered to deliver genes with enhanced efficacy by modifying the shape, chemical composition, and size. An ideal gene delivery vehicle should possess properties such as the ability to disrupt the endosomal membrane, to cross the plasma membrane, to bind, condense and protect the nucleic acid cargo, to ensure target specific delivery, have stability in circulation, and be able to evade the immune system [118,119].…”