The influence of protein corona on liposomal delivery systems: A comprehensive review

Liposomes continue to play a key role in drug delivery and diagnostics, with applications in cancer therapy and vaccine formulations. Their unique characteristics enable the development of more effective delivery systems. However, the behavior of liposomes in vivo differs significantly from their in vitro performance, which can impact their clinical application. Upon systemic administration, liposomes must circulate in the body for extended periods to reach target tissues. A challenge arises when liposomes encounter biological fluids in vivo, where proteins and other biomolecules form a "protein corona" around the liposomes, which can alter their function. Despite the development of stealth liposomes, completely preventing protein corona formation remains a challenge. The presence of the protein corona can interfere with interactions between targeting ligands and tissues, potentially reducing the efficacy of targeted delivery systems. Recent studies, however, suggest that the protein corona may also be utilized to enhance liposome functionality and targeting. This review explores the formation of the protein corona on liposomes, the factors influencing the structure and composition of liposome-protein corona complexes, and strategies to control this process. It also examines in vivo studies on protein corona formation and its impact on liposome behavior, targeting capacity, and drug release profiles. Finally, we discuss the concept of personalized liposome-protein corona complexes for the detection of disease biomarkers in vivo.