Phage-display library biopanning and bioinformatic analysis yielded a high-affinity peptide to inflamed vascular endothelium both in vitro and in vivo.
Vascular inflammation is considered the primary pathological condition occurring in many chronic diseases. To detect the inflamed endothelium via imaging analysis or guide the drug to target lesions is therefore important for early diagnosis and treatment of vascular inflammatory diseases. In this study, we obtained a novel peptide NTTTH through high throughout biopanning and bioinformatic analysis. In vitro studies indicated that NTTTH homologs could especially target inflamed vascular endothelial cells, as imaging quantitative analysis indicated that the mean of integrated optical density (MIOD) and mean of stained area (MSA) were significantly higher versus control (P<0.05). In vivo studies showed that, after intravenous injection of enhanced green fluorescent protein (EGFP)-labeled NTTTH homologs into the lipopolysaccharide (LPS)-inflamed mice for 30min, NTTTH homologs were distributed in highly vascularized and inflamed organs like liver and kidney. As a control, little fluorescence could be detected in mice injected with EGFP alone. Cryosection showed that NTTTH homologs especially targeted inflamed vasculatures but not normal ones. We did not detect fluorescence signal in either normal or inflamed mice which were injected with EGFP alone. The results suggested the role of NTTTH homologs in guiding the targeted binding of EGFP to inflamed vasculature and the potential usage for imaging detection and drug delivery.
Key Laboratory of Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University, 510515 Guangzhou, PR China; Centre of Integrated Traditional and Western Medicine on Rheumatism, General Hospital of Chengdu Military Area Command PLA, Chengdu 610083, PR China.
Min
M
Yang
Key Laboratory of Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University, 510515 Guangzhou, PR China; Department of Pathophysiology, Guangxi Medical University, 5300021 Nanning, Guangxi Province, PR China.
Chenwu
C
Liu
Key Laboratory of Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University, 510515 Guangzhou, PR China.
Maochang
M
Niu
Centre of Integrated Traditional and Western Medicine on Rheumatism, General Hospital of Chengdu Military Area Command PLA, Chengdu 610083, PR China.
Yonghe
Y
Hu
Centre of Integrated Traditional and Western Medicine on Rheumatism, General Hospital of Chengdu Military Area Command PLA, Chengdu 610083, PR China.
Mingyang
M
Guo
Centre of Integrated Traditional and Western Medicine on Rheumatism, General Hospital of Chengdu Military Area Command PLA, Chengdu 610083, PR China.
Jun
J
Zhang
Centre of Integrated Traditional and Western Medicine on Rheumatism, General Hospital of Chengdu Military Area Command PLA, Chengdu 610083, PR China.
Yong
Y
Luo
Centre of Integrated Traditional and Western Medicine on Rheumatism, General Hospital of Chengdu Military Area Command PLA, Chengdu 610083, PR China.
Weili
W
Yuan
Centre of Integrated Traditional and Western Medicine on Rheumatism, General Hospital of Chengdu Military Area Command PLA, Chengdu 610083, PR China.
Mei
M
Yang
Centre of Integrated Traditional and Western Medicine on Rheumatism, General Hospital of Chengdu Military Area Command PLA, Chengdu 610083, PR China.
Mingdong
M
Yun
Centre of Integrated Traditional and Western Medicine on Rheumatism, General Hospital of Chengdu Military Area Command PLA, Chengdu 610083, PR China.
Linling
L
Guo
Centre of Integrated Traditional and Western Medicine on Rheumatism, General Hospital of Chengdu Military Area Command PLA, Chengdu 610083, PR China.
Jiao
J
Yan
Centre of Integrated Traditional and Western Medicine on Rheumatism, General Hospital of Chengdu Military Area Command PLA, Chengdu 610083, PR China.
Defang
D
Liu
Key Laboratory of Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University, 510515 Guangzhou, PR China.
Jinghua
J
Liu
Key Laboratory of Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University, 510515 Guangzhou, PR China. Electronic address: jiang48231@163.com.
Yong
Y
Jiang
D000818:Animals; D019295:Computational Biology; D004730:Endothelium, Vascular / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000494:pharmacology*
D008070:Lipopolysaccharides; D019151:Peptide Library; D010456:Peptides, Cyclic; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
Drug guiding; Imaging detection; Peptide; Phage display; Vascular inflammatory disease