Recent Progress in Gene Delivery Systems Based on Gemini-Surfactant

Gemini surfactants (GSs) are two single-chain surfactant molecules covalently linked to their hydrophilic head groups via a spacer, resulting in a distinct structure with two hydrophilic heads and two hydrophobic tails. The GSs with cationic head groups have the potential for gene delivery by forming aggregates with negatively charged nucleic acids under the action of positive charge and self-assembly ability. Therefore, they have attracted increasing attention in the field of gene delivery. However, there remains a lack of systematic reviews summarizing various optimization strategies for GSs as gene delivery vectors in recent years. To address this gap, this review summarizes strategies for enhancing the transfection efficiency and biocompatibility of Gemini surfactant vectors, explores the relationship between their molecular structure and gene delivery performance, along with their delivery mechanism, highlights their applications in various gene delivery contexts, and discusses future development strategies and key challenges. This review provides a foundation for the further development of superior GSs, offering additional viable approaches for effective gene delivery and gene therapy of diseases.