Delivery of Nucleic Acids for Cancer Gene therapy: Overcoming extra- and intra-cellular Barriers

Abstract

The therapeutic potential of cancer gene therapy has been limited by the difficulty of delivering genetic material to target sites. Various biological and molecular barriers exist which need to be overcome before effective non-viral delivery systems can be applied successfully in oncology.Herein, various barriers are described and strategies to circumvent such obstacles are discussed, considering both the extracellular and intracellular setting. Development of multifunctional delivery systems holds much promise for the progression of gene delivery, and a growing body of evidence supports this approach involving rational design of vectors, with a unique molecular architecture. In addition, the potential application of composite gene delivery platforms is highlighted which may provide an alternative delivery strategy to traditional systemic administration.

Systemic tumor‐targeted sodium iodide symporter (NIS) gene therapy of hepatocellular carcinoma mediated by B6 peptide polyplexes

“…Interactions of particles with plasma proteins, erythrocytes or nontarget tissues, aggregation and clearance of transfection particles by the reticuloendothelial system, and the restricted extravasation of transfection particles from the bloodstream limit the availability of relevant substances in target tissues. 69 The key feature of nonviral gene delivery vehicles for systemic administration is the formation of stable and nontoxic vectors that can compact and sufficiently deliver genetic materials specifically into tumor cells with high efficiency. 70,71 LPEI (with an average molecular weight of 22 kDa), the 'gold standard' of PEI-based gene carriers, shows remarkable transfection efficiency along with a high stability of DNA complexes.…”

Preparation, characterization, and transfection efficiency of low molecular weight polyethylenimine-based nanoparticles for delivery of the plasmid encoding CD200 gene

“…4 Despite the remarkable intrinsic capability of viral gene carrier DNAs in the transfection of various genetic materials into different cells and tissues, their immunogenicity, oncogenicity, low-carrying capacity, and expensive production procedures have resulted in attempts to utilize novel non-viral gene vectors. 5,6 There are several different reports demonstrating the ability of nanoparticle-forming polymers in the delivery of nucleic acid therapeutics with high efficiency and low toxicity. Among the different polycationic compounds used in transfection, polyethylenimine (PEI) has been considered as the most extensively investigated cationic polymer due to its ability to interact with the negatively charged backbone of the nucleic acids and form nano-sized particles.…”

Delivery across the blood-brain barrier: nanomedicine for glioblastoma multiforme

“…PEG is grafted to the surface of NPs, wherein hydrophilic ethylene glycol units form associations with water molecules, resulting in the formation of a hydrated layer. This creates a physical barrier which reduces the potential for electrostatic and hydrophobic interactions, hindering protein adsorption and subsequent clearance by the MPS [64,65]. PEGylation shields the surface charge of a molecule, resulting in a more neutral surface charge as PEG content is increased [66].…”