In vivo monitoring of angiogenesis in a mouse hindlimb ischemia model using fluorescent peptide-based probes.
Vascular endothelial growth factor receptor (VEGFR) and matrix metalloproteinase (MMP) are up-regulated in ischemic tissue and play pivotal roles in promoting angiogenesis. The purpose of the present study was to evaluate two fluorophore-conjugated peptide probes specific to VEGFR and MMP for dual-targeted in vivo monitoring of angiogenesis in a murine model of hindlimb ischemia. To this end, VEGFR-Probe and MMP-Probe were developed by conjugating distinct near-infrared fluorophores to VEGFR-binding and MMP substrate peptides, respectively. VEGFR-Probe exhibited specific binding to VEGFR on HUVECs, and self-quenched MMP-Probe produced strong fluorescence intensity in the presence of MMPs in vitro. Subsequently, VEGFR-Probe and MMP-Probe were successfully utilized for time course in vivo visualization of VEGFR or MMP, respectively. Simultaneous visualization provided information regarding the spatial distribution of these proteins, including areas of co-localization. This dual-targeted in vivo imaging approach will be useful for understanding the detailed mechanism of angiogenesis and for evaluating therapeutic angiogenesis.
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul, 136-791, Republic of Korea.|Departments of Polymer Science and Chemical Engineering, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
Subin
S
Park
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul, 136-791, Republic of Korea.
Jangwook
J
Lee
Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.
Mi-Hee
MH
Jo
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul, 136-791, Republic of Korea.
Jin Hee
JH
Na
Next-generation Pharmaceutical Research Center, Korea Institute of Toxicology, Daejeon, 305-600, Republic of Korea.
Sung-Gurl
SG
Park
School of Chemical and Biological Engineering, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul, 151-744, Republic of Korea.
Hyeon-Ki
HK
Jang
Next-generation Pharmaceutical Research Center, Korea Institute of Toxicology, Daejeon, 305-600, Republic of Korea.
Sun-Woong
SW
Kang
Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.
Jong-Ho
JH
Kim
School of Chemical and Biological Engineering, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul, 151-744, Republic of Korea.
Byung-Soo
BS
Kim
Departments of Polymer Science and Chemical Engineering, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
Jae Hyung
JH
Park
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul, 136-791, Republic of Korea.|KU-KIST School, Korea University, 1 Anam-dong, Seongbuk-gu, Seoul, 136-701, Republic of Korea.
Ick Chan
IC
Kwon
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul, 136-791, Republic of Korea. jhryu@kist.re.kr.
Ju Hee
JH
Ryu
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul, 136-791, Republic of Korea. kim@kist.re.kr.
Kwangmeyung
K
Kim
D000818:Animals; D005260:Female; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D061848:Optical Imaging; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D005456:Fluorescent Dyes; D010455:Peptides
Angiogenesis; Fluorescence imaging; Matrix metalloproteinase; Molecular imaging; Vascular endothelial growth factor receptor