Tetralysine modified H-chain apoferritin mediated nucleus delivery of chemotherapy drugs synchronized with passive diffusion

Typically, the transcellular and intracellular disposal behaviors of small molecular drugs are prone to be changed, when undergo nanocarriers mediated delivery. Here, a novel approach using tetralysine modification at each subunit of H-chain apoferritin (TL-HFn) via gene recombination technology was explored to overcome the possible delayed conveyance of chemotherapy drugs, to guarantee therapeutic timing and effect. In this paper, TL-HFn was constructed by genetic modification, E. roll expression, and nickel chelate resin purification, which has the same molecular and physical properties as HFn. TL-HFn was proved to have better lysosomal escape performance in the presence of tetralysine and loading DOX into its cavity showed excellent nuclear accumulation than HFn, which was consistent with the cytotoxicity (HFn@DOX, IC50 = 4.043 +/- 0.34 mg mL(-1); TL-HFn@DOX, IC50 = 3.434 +/- 0.23 mg mL(-1)). Thus, the developed TL-HFn is an inspiring candidate for the application for the ultimate nucleus delivery chemotherapy drugs.

Automated summary

By genetically modifying H-chain apoferritin with tetralysine at each subunit to create TL-HFn, a novel approach was explored to enhance the lysosomal escape performance and nuclear accumulation of chemotherapy drugs, showing promising potential for ultimate nucleus delivery. The constructed TL-HFn demonstrated better performance in escaping lysosomes and accumulating DOX in the nucleus, indicating potential for application in delivering chemotherapy drugs effectively.