PMID- 28821462 OWN - NLM STAT- MEDLINE DCOM- 20180723 LR - 20180723 IS - 1873-4995 (Electronic) IS - 0168-3659 (Linking) VI - 267 DP - 2017 Dec 10 TI - Ferritin nanocage with intrinsically disordered proteins and affibody: A platform for tumor targeting with extended pharmacokinetics. PG - 172-180 LID - S0168-3659(17)30781-2 [pii] LID - 10.1016/j.jconrel.2017.08.014 [doi] 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. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Lee, Na Kyeong AU - Lee NK AD - Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea. FAU - Lee, Eun Jung AU - Lee EJ AD - Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Chemical Engineering, School of Applied Chemical Engineering, Kyungpook National University, Daegu 41566, Republic of Korea. FAU - Kim, Soyoun AU - Kim S AD - Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41566, Republic of Korea. FAU - Nam, Gi-Hoon AU - Nam GH AD - Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea. FAU - Kih, Minwoo AU - Kih M AD - Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea. FAU - Hong, Yeonsun AU - Hong Y AD - Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea. FAU - Jeong, Cherlhyun AU - Jeong C AD - Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea. FAU - Yang, Yoosoo AU - Yang Y AD - Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea. FAU - Byun, Youngro AU - Byun Y AD - Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea. Electronic address: yrbyun@snu.ac.kr. FAU - Kim, In-San AU - Kim IS AD - Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea. Electronic address: iskim14@kist.re.kr. LA - eng PT - Journal Article DEP - 20170815 PL - Netherlands TA - J Control Release JT - Journal of controlled release : official journal of the Controlled Release Society JID - 8607908 RN - 0 (Intrinsically Disordered Proteins) RN - 0 (Peptides) RN - 9007-73-2 (Ferritins) SB - IM MH - Animals MH - *Drug Delivery Systems MH - Ferritins/*administration & dosage/chemistry/pharmacokinetics MH - Human Umbilical Vein Endothelial Cells/drug effects/metabolism MH - Humans MH - Intrinsically Disordered Proteins/*administration & dosage/chemistry/pharmacokinetics MH - Macrophages/drug effects/metabolism MH - Mice, Inbred BALB C MH - Mice, Nude MH - Microscopy, Electron, Transmission MH - Nanostructures/*administration & dosage/chemistry/ultrastructure MH - Neoplasms/*metabolism MH - Peptides/*administration & dosage/chemistry/pharmacokinetics OTO - NOTNLM OT - Ferritin nanocages OT - Half-life OT - Intrinsically disordered protein OT - Nanomedicine OT - Pharmacokinetics EDAT- 2017/08/20 06:00 MHDA- 2018/07/24 06:00 CRDT- 2017/08/20 06:00 PHST- 2017/05/06 00:00 [received] PHST- 2017/08/12 00:00 [revised] PHST- 2017/08/14 00:00 [accepted] PHST- 2017/08/20 06:00 [pubmed] PHST- 2018/07/24 06:00 [medline] PHST- 2017/08/20 06:00 [entrez] AID - S0168-3659(17)30781-2 [pii] AID - 10.1016/j.jconrel.2017.08.014 [doi] PST - ppublish SO - J Control Release. 2017 Dec 10;267:172-180. doi: 10.1016/j.jconrel.2017.08.014. Epub 2017 Aug 15.