Simple and Efficient Targeted Intracellular Protein Delivery with Self-Assembled Nanovehicles for Effective Cancer Therapy

摘要

Protein therapy offers promising prospects for the treatment of various important diseases, thus it is highly desirable to develop a robust carrier that can deliver active proteins into cells. The development of a novel protein delivery platform based on the self-assembly of multiarmed amphiphilic cyclodextrins (CDEH) is reported. CDEH can self-assemble into nanoparticles in aqueous solution and achieve superior encapsulation of protein (loading capacity > 30% w/w) simply by mixing with protein solution without introducing any subsequent cumbersome steps that may inactivate proteins. More importantly, CDEH nanovehicles can be easily further modified with various targeting groups based on host-guest complexation. Using saporin as a therapeutic protein, AS1411-aptamer-modified CDEH nanovehicles can preferentially accumulate in tumors and efficiently inhibit tumor growth in a MDA-MB-231 xenograft mouse model. Moreover, folate-targeted CDEH nanovehicles can also deliver Cas9 protein and Plk1-targeting sgRNA into Hela cells, leading to 47.1% gene deletion and 64.1% Plk1 protein reduction in HeLa tumor tissue, thereby effectively suppressing the tumor progression. All these results indicate the potential of targeted CDEH nanovehicles in intracellular protein delivery for improving protein therapeutics.