PMID- 35295653 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220319 IS - 2296-4185 (Print) IS - 2296-4185 (Electronic) IS - 2296-4185 (Linking) VI - 10 DP - 2022 TI - VHPKQHR Peptide Modified Ultrasmall Paramagnetic Iron Oxide Nanoparticles Targeting Rheumatoid Arthritis for T(1)-Weighted Magnetic Resonance Imaging. PG - 821256 LID - 10.3389/fbioe.2022.821256 [doi] LID - 821256 AB - Magnetic resonance imaging (MRI) could be the ideal diagnostic modality for early rheumatoid arthritis (RA). Vascular cell adhesion molecule-1 (VCAM-1) is highly expressed in synovial locations in patients with RA, which could be a potential target protein for RA diagnosis. The peptide VHPKQHR (VHP) has a high affinity to VCAM-1. To make the contrast agent to target RA at an early stage, we used VHP and ultrasmall paramagnetic iron oxide (USPIO) to synthesize UVHP (U stands for USPIO) through a chemical reaction with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide. The size of UVHP was 6.7 nm; the potential was -27.7 mV, and the r (2)/r (1) value was 1.73. Cytotoxicity assay exhibited that the cell survival rate was higher than 80% at even high concentrations of UVHP (Fe concentration 200 microg/mL), which showed the UVHP has low toxicity. Compared with no TNF-alpha stimulation, VCAM-1 expression was increased nearly 3-fold when mouse aortic endothelial cells (MAECs) were stimulated with 50 ng/mL TNF-alpha; cellular Fe uptake was increased very significantly with increasing UVHP concentration under TNF-alpha treatment; cellular Fe content was 17 times higher under UVHP with Fe concentration 200 microg/mL treating MAECs. These results indicate that UVHP can target overexpression of VCAM-1 at the cellular level. RA mice models were constructed with adjuvant-induced arthritis. In vivo MRI and biodistribution results show that the signal intensity of knee joints was increased significantly and Fe accumulation in RA model mice compared with normal wild-type mice after injecting UVHP 24 h. These results suggest that we have synthesized a simple, low-cost, and less toxic contrast agent UVHP, which targeted VCAM-1 for early-stage RA diagnosis and generates high contrast in T(1)-weighted MRI. CI - Copyright (c) 2022 Zhang, Huang, Huang, Zhou, Tang, Wei, Li, Tang, Luo, Zhou and Chen. FAU - Zhang, Chunyu AU - Zhang C AD - MOE Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China. AD - Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China. AD - Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou, China. FAU - Huang, Wentao AU - Huang W AD - MOE Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China. AD - Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China. AD - Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou, China. FAU - Huang, Chen AU - Huang C AD - Department of Minimally Invasive Interventional Radiology, Guangzhou Panyu Central Hospital, Guangzhou, China. FAU - Zhou, Chengqian AU - Zhou C AD - Neuroscience Laboratory, Hugo Moser Research Institute at Kennedy Krieger, Baltimore, MD, United States. FAU - Tang, Yukuan AU - Tang Y AD - Department of Minimally Invasive Interventional Radiology, Guangzhou Panyu Central Hospital, Guangzhou, China. FAU - Wei, Wei AU - Wei W AD - Institution of GuangDong Cord Blood Bank, Guangzhou, China. FAU - Li, Yongsheng AU - Li Y AD - Institution of GuangDong Cord Blood Bank, Guangzhou, China. FAU - Tang, Yukuan AU - Tang Y AD - Department of Minimally Invasive Interventional Radiology, Guangzhou Panyu Central Hospital, Guangzhou, China. FAU - Luo, Yu AU - Luo Y AD - Shanghai Engineering Technology Research Center for Pharmaceutical Intelligent Equipment, Shanghai Frontiers Science Research Center for Druggability of Cardiovascular Noncoding RNA, Institute for Frontier Medical Technology, College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, China. FAU - Zhou, Quan AU - Zhou Q AD - Department of Radiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China. FAU - Chen, Wenli AU - Chen W AD - MOE Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China. AD - Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China. AD - Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou, China. LA - eng PT - Journal Article DEP - 20220228 PL - Switzerland TA - Front Bioeng Biotechnol JT - Frontiers in bioengineering and biotechnology JID - 101632513 PMC - PMC8918785 OTO - NOTNLM OT - USPIO OT - UVHP OT - VCAM-1 OT - magnetic resonance imaging OT - rheumatoid arthritis COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/03/18 06:00 MHDA- 2022/03/18 06:01 PMCR- 2022/01/01 CRDT- 2022/03/17 05:11 PHST- 2021/11/24 00:00 [received] PHST- 2022/01/14 00:00 [accepted] PHST- 2022/03/17 05:11 [entrez] PHST- 2022/03/18 06:00 [pubmed] PHST- 2022/03/18 06:01 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 821256 [pii] AID - 10.3389/fbioe.2022.821256 [doi] PST - epublish SO - Front Bioeng Biotechnol. 2022 Feb 28;10:821256. doi: 10.3389/fbioe.2022.821256. eCollection 2022.