Fusogenic Lipid Nanovesicles as Multifunctional Immunomodulatory Platforms for Precision Solid Tumor Therapy

Although immunotherapy demonstrates considerable prospect in overcoming solid tumors, its clinical efficacy is limited by several factors, such as poor tumor immunogenicity, inadequate immune activation, and immunosuppressive tumor microenvironment (TME). To overcome these challenges, a versatile and universal immune modulation platform should be developed, and lipid nanovesicles with membrane fusion capabilities (LNV-Fs) have attracted great attention for this purpose. By mimicking natural membrane fusion processes, LNV-Fs enable the precise presentation of immunogenic components on tumor cell membranes, effectively activating anti-tumor immune surveillance. Similarly, LNV-Fs can equip multiple functionalities on autologous and adoptive effector cells for enhanced cell therapies. Additionally, LNV-Fs function as vaccines that elicit robust autologous anti-tumor immunity while promoting long-term immune memory. Furthermore, different LNV-Fs with powerful ability in reprogramming TME have been reported. Given the recent advancements and the absence of comprehensive reviews on this topic, a comprehensive analysis of LNV-F systems, including their structural classifications, membrane fusion mechanisms, and recent applications in cancer immunotherapy is provided. Furthermore, the future prospects of LNV-Fs, with particular emphasis on artificial intelligence-assisted design are explored. This review is intended to engage researchers from diverse interdisciplinary fields and provide valuable insights for advancing precision immunotherapy.