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Abstract
High sensitivity at ultra-high field (UHF) and sufficient potential to penetrate the brain are the most desirable characteristics in the development of contrast agents (CAs) for magnetic resonance imaging (MRI). However, incorporating such qualities into a single nanocarrier is challenging. Herein, we report a new strategy for a highly brain-permeable MR CA with high sensitivity at UHF by loading dysprosium chelates (DyL) in apoferritin cavities (Apo-DyL). We also design the chelate ligand structure to increase DyL loading capacity within the apoferritin cavity. Using the intracerebroventricular (ICV) injection approach as a new delivery route for Apo-DyL, we demonstrate that apoferritin loaded with DyL can penetrate the brain-ventricular barrier and diffuse into the brain. This brain-permeable capability is unique to Apo-DyL, compared with other types of nanoparticles used in MRI. Apo-DyL also shows significant increase in MR sensitivity of DyL at UHF. Furthermore, based on brain tumor imaging at UHF, Apo-DyL can significantly enhance the tumor for a lower dose of the CA than the previously reported Gd- or Mn-loaded apoferritin nanoplatform. Therefore, Apo-DyL can be a novel nanoplatform that is a highly sensitive and versatile MR CA for UHF brain imaging.

Affiliations

Hee-Kyung Kim  1 , Ah Rum Baek  2 , Garam Choi  3 , Jung-Jin Lee  4 , Ji-Ung Yang  5 , Hoesu Jung  6 , Taekwan Lee  6 , Dongkyu Kim  6 , Minsup Kim  7 , ArtE Cho  7 , Gang Ho Lee  8 , Yongmin Chang  9
1 BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Jung-gu, Daegu, Republic of Korea; Institute of Biomedical Engineering Research, Kyungpook National University, Jung-gu, Daegu, Republic of Korea.
2 Department of Medical & Biological Engineering, Kyungpook National University, Jung-gu, Daegu, Republic of Korea.
3 Department of Medical & Biological Engineering, Kyungpook National University, Jung-gu, Daegu, Republic of Korea; Department of R&D Center, Myungmoon Bio. Co., Hwaseong, Gyeonggi-do, Republic of Korea.
4 Department of R&D Center, Myungmoon Bio. Co., Hwaseong, Gyeonggi-do, Republic of Korea.
5 Department of Medical & Biological Engineering, Kyungpook National University, Jung-gu, Daegu, Republic of Korea; Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Dong-gu, Daegu, Republic of Korea.
6 Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Dong-gu, Daegu, Republic of Korea.
7 Department of Bioinformatics, Korea University, Sejong, Republic of Korea.
8 Department of Chemistry, Kyungpook National University, Jung-gu, Daegu, Republic of Korea.
9 Department of Medical & Biological Engineering, Kyungpook National University, Jung-gu, Daegu, Republic of Korea; Department of Radiology, Kyungpook National University Hospital, Jung-gu, Daegu, Republic of Korea; Department of Molecular Medicine, School of Medicine, Kyungpook National University, Jung-gu, Daegu, Republic of Korea. Electronic address: ychang@knu.ac.kr.