Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization

Pharmaceutics

Sheng Dai¹  Bingyang Zhang²  Shuang Yin²  Jingxiu Bi²  Yiran Qu²  Yingli Wang³  Yan Wang³  Yao Zhang⁴  Yongdong Liu⁴ 

[1] Department of Chemical Engineering, Brunel University London, Uxbridge UB8 3PH, UK;School of Chemical Engineering and Advanced Materials, the University of Adelaide, Adelaide SA5005, Australia;School of Chinese Medicine and Food Engineering, Shanxi University of Traditional Chinese Medicine, Jinzhong 030619, China;State Key Laboratory of Biochemistry Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China;

关键词: ferritin;    drug delivery;    tumor targeting;    half-life extension;   

DOI  :  10.3390/pharmaceutics13040521

来源: DOAJ

【 摘 要 】

Ferritin, one of the most investigated protein nanocages, is considered as a promising drug carrier because of its advantageous stability and safety. However, its short half-life and undesirable tumor targeting ability has limited its usage in tumor treatment. In this work, two types of functional peptides, half-life extension peptide PAS, and tumor targeting peptide RGDK (Arg-Gly-Asp-Lys), are inserted to human heavy-chain ferritin (HFn) at C-terminal through flexible linkers with two distinct enzyme cleavable sites. Structural characterizations show both HFn and engineered HFns can assemble into nanoparticles but with different apparent hydrodynamic volumes and molecular weights. RGDK peptide enhanced the internalization efficiency of HFn and showed a significant increase of growth inhibition against 4T1 cell line in vitro. Pharmacokinetic study in vivo demonstrates PAS peptides extended ferritin half-life about 4.9 times in Sprague Dawley rats. RGDK peptides greatly enhanced drug accumulation in the tumor site rather than in other organs in biodistribution analysis. Drug loaded PAS-RGDK functionalized HFns curbed tumor growth with significantly greater efficacies in comparison with drug loaded HFn.

【 授权许可】

Unknown