The Intracellular Transport Pathway And Application Of The Lauric Acid Modified Protein Nanocapsules

Synthetic nanocarriers continue to play an important role in nanomedicine as the effective intracellular delivery.Better understanding of the extra-and intra-cellular fate of the nanocarriers in relation with biological environments is essential for the progress of nanocarrier-based therapeutics.Upon cellular uptake,intracellular machineries control their trafficking,release and degradation of cargoes.Drug-loaded polymer nanocapsules have potential applications in the field of drug delivery systems.Natural and synthetic commonly used to prepare nanomaterials.Among them,nano-precipitation method,emulsification diffusion method and double emulsification method,emulsion adhesive and self-assembly method can be used to prepare polymer nanocapsules.Protein nanocapsules,as an intracellular delivery platform,have exhibited promising potential applications in the field of protein drug delivery.However,escape the endo-lysosome and auto-lysosome system is critical to perform the function of protein drugs.Natural protein cytotoxins perform this task with outstanding efficacy.They enter cells with receptor-targeted specificity,respond to changing intracellular microenvironments,and by various mechanisms translocate their cytotoxic protein subunit into the cytosol.Here,we prepared protein nanocapsules based on BSA(nBSA)and lauric acid modified nanocapsules(LA-nBSA)to investigate the escape effect from the endosome and autophgosome.They uptake by the cells mainly through Arf-6-dependent endocytosis and Rab34-mediated micropinocytosis.nBSA transported Rab7 and LC3 positive endosome and autophagy pathway.LA-nBSA could efficiently escape from the endosome and autophagy pathway form the degradation by lysosome.In conclusion,the lauric acid modified protein nanocapsules can enhance the stability,less susceptible to enzyme degradation or protein types,enhance protein break away from the cell body.Our findings give us a better understanding of the development of the protein drug delivery platform and the treatment of related diseases.