PMID- 35631669 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 1999-4923 (Print) IS - 1999-4923 (Electronic) IS - 1999-4923 (Linking) VI - 14 IP - 5 DP - 2022 May 18 TI - Targeting Peptide, Fluorescent Reagent Modified Magnetic Liposomes Coated with Rapamycin Target Early Atherosclerotic Plaque and Therapy. LID - 10.3390/pharmaceutics14051083 [doi] LID - 1083 AB - Atherosclerosis is the leading cause of global morbidity and mortality. Its therapy requires research in several areas, such as diagnosis of early arteriosclerosis, improvement of the pharmacokinetics and bioavailability of rapamycin as its therapeutic agents. Here, we used the targeting peptide VHPKQHR (VHP) (or fluorescent reagent) to modify the phospholipid molecules to target vascular cell adhesion molecule-1 (VCAM-1) and loaded ultrasmall paramagnetic iron oxide (USPIO/Fe(3)O(4)) plus rapamycin (Rap) to Rap/Fe(3)O(4)@VHP-Lipo (VHPKQHR-modified magnetic liposomes coated with Rap). This nanoparticle can be used for both the diagnosis and therapy of early atherosclerosis. We designed both an ex vivo system with mouse aortic endothelial cells (MAECs) and an in vivo system with ApoE knockout mice to test the labeling and delivering potential of Rap/Fe(3)O(4)@VHP-Lipo with fluorescent microscopy, flow cytometry and MRI. Our results of MRI imaging and fluorescence imaging showed that the T2 relaxation time of the Rap/Fe(3)O(4)@VHP-Lipo group was reduced by 2.7 times and 1.5 times, and the fluorescence intensity increased by 3.4 times and 2.5 times, respectively, compared with the normal saline group and the control liposome treatment group. It showed that Rap/Fe(3)O(4)@VHP-Lipo realized the diagnosis of early AS. Additionally, our results showed that, compared with the normal saline and control liposomes treatment group, the aortic fluorescence intensity of the Rap/Fe(3)O(4)@VHP-Lipo treatment group was significantly weaker, and the T2 relaxation time was prolonged by 8.9 times and 2.0 times, indicating that the targeted diagnostic agent detected the least plaques in the Rap/Fe(3)O(4)@VHP-Lipo treatment group. Based on our results, the synthesized theragnostic Rap/Fe(3)O(4)@VHP-Lipo serves as a great label for both MRI and fluorescence bimodal imaging of atherosclerosis. It also has therapeutic effects for the early treatment of atherosclerosis, and it has great potential for early diagnosis and can achieve the same level of therapy with a lower dose of Rap. FAU - Huang, Chen AU - Huang C AD - Department of Minimally Invasive Interventional Radiology, Guangzhou Panyu Central Hospital, Guangzhou 511400, China. FAU - Huang, Wentao AU - Huang W AUID- ORCID: 0000-0002-2257-4502 AD - MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. AD - Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. AD - Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China. FAU - Zhang, Lifen AU - Zhang L AD - MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. AD - Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. AD - Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China. 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 510631, China. AD - Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. AD - Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China. FAU - Zhou, Chengqian AU - Zhou C AD - Neuroscience Laboratory, Hugo Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA. FAU - Wei, Wei AU - Wei W AD - Institution of Guang Dong Cord Blood Bank, Guangzhou 510700, China. FAU - Li, Yongsheng AU - Li Y AD - Institution of Guang Dong Cord Blood Bank, Guangzhou 510700, China. FAU - Zhou, Quan AU - Zhou Q AD - Department of Radiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China. FAU - Chen, Wenli AU - Chen W AUID- ORCID: 0000-0002-4768-3844 AD - MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. AD - Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. AD - Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China. FAU - Tang, Yukuan AU - Tang Y AD - Department of Minimally Invasive Interventional Radiology, Guangzhou Panyu Central Hospital, Guangzhou 511400, China. LA - eng GR - 81471659/National Natural Science Foundation of China/ GR - 202103000002/Guangzhou Science and Technology Planning Project/ GR - B2021376/Guangdong Medical Science and Technology Research Foundation/ GR - 2020-Z04-002/Panyu Major Science and Technology Planning Project/ GR - 201805010002/the Science and Technology Project of Guangzhou/ PT - Journal Article DEP - 20220518 PL - Switzerland TA - Pharmaceutics JT - Pharmaceutics JID - 101534003 PMC - PMC9146689 OTO - NOTNLM OT - MRI OT - Rap/Fe3O4@VHP-Lipo OT - VCAM-1 OT - bimodal imaging OT - early atherosclerosis OT - rapamycin COIS- The authors declare no conflict of interest. EDAT- 2022/05/29 06:00 MHDA- 2022/05/29 06:01 PMCR- 2022/05/18 CRDT- 2022/05/28 01:39 PHST- 2022/04/05 00:00 [received] PHST- 2022/05/09 00:00 [revised] PHST- 2022/05/16 00:00 [accepted] PHST- 2022/05/28 01:39 [entrez] PHST- 2022/05/29 06:00 [pubmed] PHST- 2022/05/29 06:01 [medline] PHST- 2022/05/18 00:00 [pmc-release] AID - pharmaceutics14051083 [pii] AID - pharmaceutics-14-01083 [pii] AID - 10.3390/pharmaceutics14051083 [doi] PST - epublish SO - Pharmaceutics. 2022 May 18;14(5):1083. doi: 10.3390/pharmaceutics14051083.