Physicochemical properties of polymers: An important system to overcome the cell barriers in gene transfection

Abstract

Delivery of the macromolecules including DNA, miRNA, and antisense oligonucleotides is typically mediated by carriers due to the large size and negative charge. Different physical (e.g., gene gun or electroporation), and chemical (e.g., cationic polymer or lipid) vectors have been already used to improve the efficiency of gene transfer. Polymer-based DNA delivery systems have attracted special interest, in particular via intravenous injection with many intra- and extracellular barriers. The recent progress has shown that stimuli-responsive polymers entitled as multifunctional nucleic acid vehicles can act to target specific cells. These nonviral carriers are classified by the type of stimulus including reduction potential, pH, and temperature. Generally, the physicochemical characterization of DNA-polymer complexes is critical to enhance the transfection potency via protection of DNA from nuclease digestion, endosomal escape, and nuclear localization. The successful clinical applications will depend on an exact insight of barriers in gene delivery and development of carriers overcoming these barriers. Consequently, improvement of novel cationic polymers with low toxicity and effective for biomedical use has attracted a great attention in gene therapy. This article summarizes the main physicochemical and biological properties of polyplexes describing their gene transfection behavior, in vitro and in vivo. In this line, the relative efficiencies of various cationic polymers are compared.

Applications of polymer-based nanoparticles in vaccine field

“…PEG has been used to coat PLA nanoparticles, and it usually aggrandizes the solubility of nanoparticles, decreasing their aggregation and interaction with proteins in physiological fluids. This produces spatial stability on the surface of the gene carrier to enhance transfer efficiency [45]. Compared to the bulk materials and microparticles, nanoparticles exhibit different mechanical properties.…”

Different strategies of gene delivery for treatment of cancer and other disorders

“…The structural diversity in polymers for gene delivery contains cationic residues, endosomal escape units, and degradable fragments. [29,30] Some examples of polymers such as Chitosan, Gelatin, Polyethylene imine (PEI), Poly lactic-co-glycolic acid (PLGA) and poly lactic acid (PLA), Dendrimers were described as following.…”

Comparison of the cellular transport mechanism of cationic, star-shaped polymers and liposomes in HaCat cells

“…Past research has shown that to achieve successful transfection, nonviral delivery systems, such as those delivering siRNA, need to overcome several cellular barriers, including being internalized by cells, escaping from endolysosomes, and dissociating the cargo from the complex for delivery into the cytoplasm. 3 Endocytosis has been established as the main mechanism for the uptake of nonviral vectors into the cells. 4 Endocytosis can be classified into five categories: phagocytosis, clathrin-dependent endocytosis (CDE), caveolae-mediated endocytosis (Cav-ME), non-clathrin-and non-caveolae dependent endocytosis, and macropinocytosis.…”