Immune Activities of Polycationic Vectors for Gene Delivery

Abstract

Polycationic vectors are used widely in the field of gene delivery, while currently their immune activities in vivo are poorly understood. In this comprehensive review, we aim to present an overview of existing mechanisms of adverse immune responses induced by the polycation/gene complexes, which includes the polycations themselves, the gene sequences and the ROS produced by them. These causes can induce pro-inflammatory cytokines, hypersensitivity as well as the activation of toll-like receptors, and finally the immunostimulation occur. In addition, we introduce some different opinions and research results on the immunogenicity of classical polycations such as polylysine (PLL), polyethyleneimine (PEI), polyamidoamine dendrimers (PAMAM), chitosan and gelatin, most of which have immunogenicity and can induce immunoreactions in vivo. The methods now used to adjust their immunogenicity are shown in the final part of this review. Nowadays, there is still no accurate conclusion on immunogenicity of polycations, which confuses researchers seriously in in vivo test. We conclude that further research is needed in order to skillfully utilize or inhibit the immunogenicity of these polycationic vectors.

Cationic Nanoparticle-Based Cancer Vaccines

“…These holes could be formed by the hydrolysis of cell-membrane phospholipids, mediated by the cationic groups in the polymers. An increase in the degree of cationic groups was related to increasing immune stimulating capacity [ 27 , 43 , 154 , 155 , 156 ].…”

Characterization of an Amphiphilic Phosphonated Calixarene Carrier Loaded With Carboplatin and Paclitaxel: A Preliminary Study to Treat Colon Cancer in vitro and in vivo

“…Nanomedicine encompasses the application of nanotechnology (construction of functional structures on the nanometer scale) to the treatment, diagnosis, monitoring, and control of biological systems (Yang et al, 2015; Li et al, 2019; Wei et al, 2019). This field has seen the development of a number of drug delivery platforms, including polymer-drug conjugates (Li and Wallace, 2008; Karolczak-Bayatti et al, 2019), liposomes (Paasonen et al, 2010; Shen and Ye, 2019), micelles (Dehghan Kelishady et al, 2014; Alliot et al, 2019), nanoshells (Huschka et al, 2012; Russo et al, 2019), and dendrimers (Modi et al, 2014; Zhao et al, 2017). The overarching aim of nanomedicine development is to design more specific drug delivery and targeting therapies as alternatives to conventional therapies.…”

Polycations for Gene Delivery: Dilemmas and Solutions

“…Several other strategies also have great potential to reduce the toxicity of cationic polymer-mediated gene delivery, including introduction of PEG segments, cross-linking via reducible bonds, and introduction of hydrophobic or hydrophilic segments. 85,107 ■ CONCLUSIONS AND FUTURE PERSPECTIVES In summary, a comprehensive understanding of the "dilemmas" in gene therapy can guide the design of more intelligent carriers (Table 1). With rapid developments in nanotechnology and biological sciences, the comprehensive route of gene delivery systems entering target cells and realization of their functions will be further clarified.…”