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Nanoparticle-Mediated Small RNA Deliveries for Molecular Therapies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Ramasamy Paulmurugan, Uday Kumar Sukumar, Tarik F. Massoud
In one study, a lipoplex for delivering siRNA targeting VE-cadherin in the endothelial cells was developed by using E-selectin targeted antibody conjugated cationic lipid (anti-E-selectin–SAINT lipoplex (SAINTarg)). It effectively transfected human umbilical vein endothelial cells (HUVECs) and showed biological function by downregulating E-cadherin expression [8]. Lipids such as 1,2-di-O-octadecenyl-3-trimethylammonium (DOTMA), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and dioleoylphosphatidylethanolamine (DOPE) are commonly used for making lipoplexes for transfection of nucleic acids, including siRNAs. Addition of cholesterol to lipoplexes makes these lipids deliver the loaded siRNAs into cells without encountering endosomes. This process is also called a fusogenic delivery mechanism [9]. PEGylated DC-Chol/DOPE liposomes loaded with siRNA targeting kinesin spindle protein (KSP) has shown an enhanced anticancer property against ovarian cancer in a preclinical mouse model without activating the immune system [10]. The use of polyethylene glycol (PEG) with lipids in lipoplex preparations has shown improved biodistribution of loaded siRNAs in the circulation, which facilitated improved tumor specific uptake in vivo. However, the use of PEG in lipoplexes can reduce the amount of siRNAs that can be complexed with the lipids [11].
The non-viral vectors and main methods of loading siRNA onto the titanium implants and their application
Published in Journal of Biomaterials Science, Polymer Edition, 2020
Liangrui Chen, Mingxuan Bai, Ruiyu Du, Hao Wang, Yi Deng, Anqi Xiao, Xueqi Gan
The liposome is a closed vesicle composed of two molecular layers, and the carried target gene is introduced into the cell by the endocytosis or phagocytosis of it. The lipid complex is not immunogenic, the tissue toxicity is weak and preparation of the transfection liposome is easy, so the liposome transfection has become one of the most common methods for gene transfer today [18]. The types of nucleic acid/liposome complexes for liposome transfection are mainly four: negatively charged liposomes, immunoliposomes, ligand liposomes and cationic liposomes. The cationic liposome is one of the most detailed transfection liposomes in the present study, while DOTMA and DOTAP are two mainly used cationic liposomes [51]. The cationic liposome consists of three parts: hydrophobic lipid group, linking group and head group. The positive charge liposome is adsorbed on the polynuclear acid to form an aggregate, and with the increasing of the lipid mass, the DNA is gradually folded and concentrated and the final nucleic acid is covered by the lipid double layer [52]. The advantages of liposomes transfer technology are mainly manifested in the low toxicity, no special requirements for the size of nucleic acids carried, and easy to prepare a large number of nucleic acids. More importantly, the immunogenicity of lipid vectors is usually low, which allows the use of the same vector in vivo as in vitro [53].