Delivery of oligonucleotides with lipid nanoparticles

Abstract

Since their inception in the 1980's, oligonucleotide-based (ON-based) therapeutics have been recognized as powerful tools that can treat a broad spectrum of diseases. The discoveries of novel regulatory methods of gene expression with diverse mechanisms of action are still driving the development of novel ON-based therapeutics. Difficulties in the delivery of this class of therapeutics hinder their in vivo applications, which forces drug delivery systems to be a prerequisite for clinical translation. This review discusses the strategy of using lipid nanoparticles as carriers to deliver therapeutic ONs to target cells in vitro and in vivo. A discourse on how chemical and physical properties of the lipid materials could be utilized during formulation and the resulting effects on delivery efficiency constitutes the major part of this review.

Cargo-Free Nanoparticles Containing Cationic Lipids Induce Reactive Oxygen Species and Cell Death in HepG2 Cells

“…1) As a cargo of these NPs, small-interfering RNAs (siRNAs) are frequently adopted as an effective strategy for cancer treatment due to their suppression of cancerrelated gene (e.g., c-Myc) expression.…”

Recent applications of the combination of mesoporous silica nanoparticles with nucleic acids: development of bioresponsive devices, carriers and sensors

“…117,118 This strategy, although does not ensure an outstanding preservation, is highly versatile and suitable for these purposes. For instance, there have been reported successful nonviral siRNAs deliveries with other systems like polymers, 119,120 peptides, 121 dendrimers, 122 lipids, 123 or metallic nanoparticles 124 among many other systems. 125,126 In fact, the use of hybrid carriers containing polycationic fragments also enables the combination of features from both components.…”

Antisense Oligonucleotides as Therapeutics and their Delivery

“…Various in vivo studies indicated that cationic liposomes show fast serum clearance and adsorption of anionic serum proteins on them, which cause early release of therapeutics. Surface coating of cationic liposomes with PEG (polyethylene glycol) demonstrated better colloidal stability and extended blood circulation half-life 20 . Although cationic lipids have higher encapsulation efficiency, their use as a delivery vehicle is limited because they are cytotoxic in nature.…”

“…(ii) Formation of ion-pairs with cationic lipids due to the diffusion of anionic lipids of the cell membrane into the cationic lipoplexes. (iii) Displacement by anionic lipids and release of As-ODNs into the cytoplasm 20,21 . In vitro studies were performed on G6 glioma cell line.…”