Polyethyleneimine-Based Lipopolyplexes as Carriers in Anticancer Gene Therapies

Abstract

Recent years have witnessed rapidly growing interest in application of gene therapies for cancer treatment. However, this strategy requires nucleic acid carriers that are both effective and safe. In this context, non-viral vectors have advantages over their viral counterparts. In particular, lipopolyplexes—nanocomplexes consisting of nucleic acids condensed with polyvalent molecules and enclosed in lipid vesicles—currently offer great promise. In this article, we briefly review the major aspects of developing such non-viral vectors based on polyethyleneimine and outline their properties in light of anticancer therapeutic strategies. Finally, examples of current in vivo studies involving such lipopolyplexes and possibilities for their future development are presented.

A Review of Different Types of Liposomes and Their Advancements as a Form of Gene Therapy Treatment for Breast Cancer

“…When a higher molecular weight polymer or an increase in N/P ratio is used, the selectivity and efficacy of the carrier to transfer genes will be reduced [ 91 ]. Though this type of formulation shows promising results in vitro, it is not entirely successful when administered in vitro due to its low stability when stored or exposed to salt and serum within a biological system or environment [ 92 , 93 ]. To sum it up, anionic liposomes are more stable in a biological environment than cationic liposomes.…”

“…It also has the potential for high transfection efficiency due to escaping the endosomal pathway with direct fusion into the cell membrane and releasing its cargo into the cytosol. Despite all these good traits, using anionic lipids on a large industrial scale is highly impossible as it is very complex (relying heavily on immunolocalisation tests, which frequently fail due to membrane integrity losses), and its production cost is very high [ 93 ].…”

“…However, formulating PEI into an anionic liposome is challenging as different molecular weights of PEI will give different outcomes to the carrier cytotoxicity. According to Ewe et al [ 92 ] and Jerzykiewicz et al [ 93 ], certain low-molecular-weight linear PEIs have significant efficacy and minimal cytotoxicity to be successfully incorporated into liposome formulation compared to higher-molecular weight PEIs [ 92 , 93 ].…”

A perspective on oligonucleotide therapy: Approaches to patient customization

“…Lipopolyplexes are nano complexes composed of lipoplexes, polycations (peptides or polymers), and nucleic acids. Due to their high specificity, biocompatibility and versatility, lipopolyplexes are being developed for different therapeutic needs ( Rezaee et al, 2016 ; Jerzykiewicz and Czogalla, 2021 ).…”

Polyethyleneimine-based immunoadjuvants for designing cancer vaccines

“…16,18 As a new class of synthesized materials, PEI has emerged as a suitable carrier and an immunoadjuvant for antigens to generate a durable immune response. 33,38,[41][42][43][44] In the following sections, we have discussed the key regulatory issues associated with PEI-based vaccines.…”