PubAg

Main content area

Extending Half Life of H-Ferritin Nanoparticle by Fusing Albumin Binding Domain for Doxorubicin Encapsulation

Author:
Wang, Chunyue, Zhang, Chun, Li, Zenglan, Yin, Shuang, Wang, Qi, Guo, Fangxia, Zhang, Yao, Yu, Rong, Liu, Yongdong, Su, Zhiguo
Source:
Biomacromolecules 2018 v.19 no.3 pp. 773-781
ISSN:
1526-4602
Subject:
Escherichia coli, binding capacity, doxorubicin, encapsulation, ferritin, half life, human serum albumin, humans, models, nanoparticles, particle size, pharmacokinetics, rats, therapeutics
Abstract:
Nanoparticles based on the heavy chain of the human ferritin (HFn) are arousing growing interest in the field of drug delivery due to their exceptional characteristics. However, the unsatisfied plasma half life of HFn substantially limits its application as a delivery platform for antitumor agents. Herein we fused an albumin binding domain (ABD) variant that basically derives from the streptococcal protein G and possesses a long-acting characteristic in serum albumin to the N-terminus of the HFn for the aim of half-life extension. This ABD–HFn construct was highly expressed and fully self-assembled into symmetrical and spherical structure in E. coli bacteria. The purified ABD–HFn showed a similar particle size with wild-type HFn and also exhibited an extremely high binding affinity with human serum albumin. To evaluate the therapeutic potential of this ABD–HFn construct in terms of half-life extension, we encapsulated a model antitumor agent doxorubicin (DOX) into the ABD–HFn. Significantly outstanding loading efficacy of above 60 molecules doxorubicin for each ABD–HFn cage was achieved. The doxorubicin-loaded ABD–HFn nanoparticle was characterized and further compared with the recombinant HFn counterpart. The ABD–HFn/DOX nanoparticle showed dramatically improved stability and comparable cell uptake rate when compared with HFn/DOX counterpart. Pharmacokinetics study in Sprague–Dawley rats showed that ABD–HFn/DOX nanoparticle possessed significantly prolonged plasma half life of ∼17.2 h, exhibiting nearly 19 times longer than that of free doxorubicin and 12 times for HFn/DOX. These optimal results indicated that fusion with ABD will be a promising strategy to extend the half life for protein-based nanoparticles.
Agid:
5987177