Exploring the promise of lipoplexes: From concept to clinical applications

Lipoplexes are non-viral lipid vectors that effectively form complexes with genetic material, positioning them as promising alternatives to viral vectors in gene therapy. Their advantages include lower toxicity, reduced immunogenicity, improved targetability, and ease of large-scale production. A typical lipoplex is composed of cationic lipids, neutral lipids, and anionic nucleic acids (e.g., DNA, mRNA, miRNA, siRNA, shRNA). Neutral lipids play an auxiliary role and are often used as transfection enhancers. Enhancing lipoplex efficiency often involves modifying the cationic lipid structure through functional groups like PEG polymers and targeting ligands. The assembly of lipoplexes occurs spontaneously. This process involves the binding of the positively charged polar head group of the cationic lipid to the negatively charged DNA spontaneously as a result of electrostatic interaction, then irreversible rearrangement and condensation of the lipoplex occurs to form either lamellar or hexagonal structures. The transfection process encompasses several steps: cellular entry, endosomal escape and cargo release, cytoplasmic trafficking, and nuclear entry. The physicochemical and biological properties of lipoplexes are influenced by factors such as lipid structure, charge ratio, and environmental conditions. Despite certain limitations like low gene transfer efficiency and rapid clearance by serum proteins, lipoplexes show promise for clinical applications. They can be administered through various routes, offering potential treatments for diseases such as cancer, bone damage, infection, and cystic fibrosis. The study aims to examine the potential of lipoplexes as a promising vehicle for delivering therapeutic agents and their progression from theoretical concepts to practical clinical applications.