Learn from nature: Biomimetic nanocarriers for intracellular protein delivery

Nanocarriers have been regarded as the most potential therapeutic weapons to combat tumors and genetic diseases using protein drugs. However, nanocarriers often face many challenges during the delivery process. Due to the existence of cell membrane barriers, nanocarriers may be restricted extracellularly or degraded in lysosomes, thus unable to effectively deliver drugs to the target location. The biomimetic nanocarrier delivery systems have demonstrated unique advantages in the field of protein delivery. This review focuses on cutting-edge technologies such as biomimetic mineralized nanoparticles, Virus-like particles, and bacterium-like nanoparticles. These biomimetic nanocarriers exhibit great potential to bypass endocytosis and lysosomal restrictions due to their unique biomimetic properties. Additionally, this review reviews the latest progress of cytosolic protein drug delivery systems based on biomimetic systems in various medical research and clinical applications, including clinical targeted delivery, tumor therapy, and gene editing. It also compares the capabilities and limitations of these biomimetic cytosolic protein delivery systems with traditional nanocarriers, including factors that affect protein delivery efficiency, and emphasizes their potential to adopt targeted, sustainable, and minimally invasive treatment methods. Finally, this review proposes the current limitations and future research directions of protein delivery systems, expecting to provide more efficient solutions for disease treatment.