TY - JOUR
T1 - Ferritin nanocage with intrinsically disordered proteins and affibody
T2 - A platform for tumor targeting with extended pharmacokinetics
AU - Lee, Na Kyeong
AU - Lee, Eun Jung
AU - Kim, Soyoun
AU - Nam, Gi hoon
AU - Kih, Minwoo
AU - Hong, Yeonsun
AU - Jeong, Cherlhyun
AU - Yang, Yoosoo
AU - Byun, Youngro
AU - Kim, In San
N1 - Funding Information:
N.K.L and E.J.L contributed equally to this work. This work was supported by grants from the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT & Future Planning (MSIP) (No. 2015R1A2A1A15056039 & NRF-2017R1A3B1023418); the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1420390); and the KIST Intramural Funding.
Funding Information:
N.K.L and E.J.L contributed equally to this work. This work was supported by grants from the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT & Future Planning (MSIP) (No. 2015R1A2A1A15056039 & NRF-2017R1A3B1023418 ); the National R&D Program for Cancer Control , Ministry of Health and Welfare , Republic of Korea ( 1420390 ); and the KIST Intramural Funding .
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/12/10
Y1 - 2017/12/10
N2 - Ferritin nanocages are of particular interest as a novel platform for drug and vaccine delivery, diagnosis, biomineralization scaffold and more, due to their perfect and complex symmetry, ideal physical properties, high biocompatibility, low toxicity profiles as well as easy manipulation by genetic or chemical strategies. However, a short half-life is still a hurdle for the translation of ferritin-based nanomedicines into the clinic. Here, we developed a series of rationally designed long circulating ferritin nanocages (LCFNs) with ‘Intrinsically Disordered Proteins (IDP)’ as a stealth layer for extending the half-life of ferritin nanocages. Through predictions with 3D modelling, the LCFNs were designed, generated and their pharmacokinetic parameters including half-life, clearance rate, mean residence time, and more, were evaluated by qualitative and quantitative analysis. LCFNs have a tenfold increased half-life and overall improved pharmacokinetic parameters compared to wild-type ferritin nanocages (wtFN), corresponding to the low binding against bone marrow-derived macrophages (BMDMs) and endothelial cells. Subsequently, a tumor targeting moiety, epidermal growth factor receptor (EGFR)-targeting affibody peptide, was fused to LCFNs for evaluating their potential as a theragnostic platform. The tumor targeting-LCFNs successfully accumulated to the tumor tissue, by efficient targeting via active and passive properties, and also the shielding effect of IDP in vivo. This strategy can be applied to other protein-based nanocages for further progressing their use in the field of nanomedicine.
AB - Ferritin nanocages are of particular interest as a novel platform for drug and vaccine delivery, diagnosis, biomineralization scaffold and more, due to their perfect and complex symmetry, ideal physical properties, high biocompatibility, low toxicity profiles as well as easy manipulation by genetic or chemical strategies. However, a short half-life is still a hurdle for the translation of ferritin-based nanomedicines into the clinic. Here, we developed a series of rationally designed long circulating ferritin nanocages (LCFNs) with ‘Intrinsically Disordered Proteins (IDP)’ as a stealth layer for extending the half-life of ferritin nanocages. Through predictions with 3D modelling, the LCFNs were designed, generated and their pharmacokinetic parameters including half-life, clearance rate, mean residence time, and more, were evaluated by qualitative and quantitative analysis. LCFNs have a tenfold increased half-life and overall improved pharmacokinetic parameters compared to wild-type ferritin nanocages (wtFN), corresponding to the low binding against bone marrow-derived macrophages (BMDMs) and endothelial cells. Subsequently, a tumor targeting moiety, epidermal growth factor receptor (EGFR)-targeting affibody peptide, was fused to LCFNs for evaluating their potential as a theragnostic platform. The tumor targeting-LCFNs successfully accumulated to the tumor tissue, by efficient targeting via active and passive properties, and also the shielding effect of IDP in vivo. This strategy can be applied to other protein-based nanocages for further progressing their use in the field of nanomedicine.
KW - Ferritin nanocages
KW - Half-life
KW - Intrinsically disordered protein
KW - Nanomedicine
KW - Pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=85028079317&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2017.08.014
DO - 10.1016/j.jconrel.2017.08.014
M3 - Article
C2 - 28821462
AN - SCOPUS:85028079317
SN - 0168-3659
VL - 267
SP - 172
EP - 180
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -