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 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

Modified Gold Nanoparticles for Efficient Delivery of Betulinic Acid to Cancer Cell Mitochondria

“…It is de-fined as the magnitude of the electrostatic potential generated on the edge of the slipping plane between the particle and the dispersant medium. The NP interacts with the ions in the dispersant medium [ 52 , 53 ]. The zeta potential is a good measure of NP stability, with values of ±20 mV irrespective of charge being regarded as highly stable.…”

“…T-Au-PEG and T-Au-[PLL-g-PEG] recorded high zeta potential values of −23.1 and +23.4 mV, respectively, suggesting stability and low tendency for agglomeration. Since NPs with positive zeta potentials are assumed to interact favorably with anionic cell membranes, it is also possible for NPs with negative zeta potential to enter cells and induce their therapeutic activity [ 53 ]. The polydispersity index (PDI) provides us with an indication of the uniformity of a particle size in solution.…”

The Twofold Role of Osteogenic Small Molecules in Parkinson’s Disease Therapeutics: Crosstalk of Osteogenesis and Neurogenesis

“…Drug nanocarriers enhances bioavailability, solubility, chemical stability, biodegradation, circulation half-life, ease of surface targeting, and permeation of drug while decreases effective dose resulting in less side effects in other tissue and organs [ 53 , 54 ]. For example, lipid nanoparticles containing cholesterol improve the stability of drug and cell-membrane fusion [ 55 ]. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have some advantage compared to the liposomes such as higher loading capacity, bioavailability, and control on drug release while SLN during the time crystallize in storage site and expulse the drug.…”