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.
Conclusion
This anti- c-myc MS09:Chol lipoplex exemplifies a simple anticancer agent with enhanced c-myc gene silencing potential in vitro.
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.