TY - JOUR
T1 - Near-Infrared Emitting Ir(III) Complexes Bearing a Dipyrromethene Ligand for Oxygen Imaging of Deeper Tissues In Vivo
AU - Mizukami, Kiichi
AU - Muraoka, Takako
AU - Shiozaki, Shuichi
AU - Tobita, Seiji
AU - Yoshihara, Toshitada
N1 - Funding Information:
This research was supported by JSPS KAKENHI (Grant Number: JP 19K22947 to T.Y. and JP 18H03509 to S.T.), the Shimadzu Science Foundation, the Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering, and a Grant-in-Aid for Scientific Research on Innovative Areas (No. 26111012 to S.T.). The authors thank the Center for Instrumental Analysis, Gunma University, for the measurements of 1H NMR, 13C NMR, and ESI-MS spectra, and the Organization for Research Initiative and Promotion, Tottori University, for the measurements of high-resolution mass spectra. They also thank Prof. Takeshi Inagaki for providing AML12 cells.
Funding Information:
This research was supported by JSPS KAKENHI (Grant Number: JP 19K22947 to T.Y. and JP 18H03509 to S.T.), the Shimadzu Science Foundation, the Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering, and a Grant-in-Aid for Scientific Research on Innovative Areas (No. 26111012 to S.T.). The authors thank the Center for Instrumental Analysis, Gunma University, for the measurements of H NMR, C NMR, and ESI-MS spectra, and the Organization for Research Initiative and Promotion, Tottori University, for the measurements of high-resolution mass spectra. They also thank Prof. Takeshi Inagaki for providing AML12 cells. 1 13
Publisher Copyright:
© 2022 American Chemical Society
PY - 2022/2/15
Y1 - 2022/2/15
N2 - Phosphorescence lifetime imaging microscopy (PLIM) using a phosphorescent oxygen probe is an innovative technique for elucidating the behavior of oxygen in living tissues. In this study, we designed and synthesized an Ir(III) complex, PPYDM-BBMD, that exhibits long-lived phosphorescence in the near-infrared region and enables in vivo oxygen imaging in deeper tissues. PPYDM-BBMD has a π-extended ligand based on a meso-mesityl dipyrromethene structure and phenylpyridine ligands with cationic dimethylamino groups to promote intracellular uptake. This complex gave a phosphorescence spectrum with a maximum at 773 nm in the wavelength range of the so-called biological window and exhibited an exceptionally long lifetime (18.5 μs in degassed acetonitrile), allowing for excellent oxygen sensitivity even in the near-infrared window. PPYDM-BBMD showed a high intracellular uptake in cultured cells and mainly accumulated in the endoplasmic reticulum. We evaluated the oxygen sensitivity of PPYDM-BBMD phosphorescence in alpha mouse liver 12 (AML12) cells based on the Stern-Volmer analysis, which gave an O2-induced quenching rate constant of 1.42 × 103 mmHg-1 s-1. PPYDM-BBMD was administered in the tail veins of anesthetized mice, and confocal one-photon PLIM images of hepatic tissues were measured at different depths from the liver surfaces. The PLIM images visualized the oxygen gradients in hepatic lobules up to a depth of about 100 μm from the liver surfaces with a cellular-level resolution, allowing for the quantification of oxygen partial pressure based on calibration results using AML12 cells.
AB - Phosphorescence lifetime imaging microscopy (PLIM) using a phosphorescent oxygen probe is an innovative technique for elucidating the behavior of oxygen in living tissues. In this study, we designed and synthesized an Ir(III) complex, PPYDM-BBMD, that exhibits long-lived phosphorescence in the near-infrared region and enables in vivo oxygen imaging in deeper tissues. PPYDM-BBMD has a π-extended ligand based on a meso-mesityl dipyrromethene structure and phenylpyridine ligands with cationic dimethylamino groups to promote intracellular uptake. This complex gave a phosphorescence spectrum with a maximum at 773 nm in the wavelength range of the so-called biological window and exhibited an exceptionally long lifetime (18.5 μs in degassed acetonitrile), allowing for excellent oxygen sensitivity even in the near-infrared window. PPYDM-BBMD showed a high intracellular uptake in cultured cells and mainly accumulated in the endoplasmic reticulum. We evaluated the oxygen sensitivity of PPYDM-BBMD phosphorescence in alpha mouse liver 12 (AML12) cells based on the Stern-Volmer analysis, which gave an O2-induced quenching rate constant of 1.42 × 103 mmHg-1 s-1. PPYDM-BBMD was administered in the tail veins of anesthetized mice, and confocal one-photon PLIM images of hepatic tissues were measured at different depths from the liver surfaces. The PLIM images visualized the oxygen gradients in hepatic lobules up to a depth of about 100 μm from the liver surfaces with a cellular-level resolution, allowing for the quantification of oxygen partial pressure based on calibration results using AML12 cells.
UR - http://www.scopus.com/inward/record.url?scp=85124285635&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85124285635&partnerID=8YFLogxK
U2 - 10.1021/acs.analchem.1c04271
DO - 10.1021/acs.analchem.1c04271
M3 - Article
AN - SCOPUS:85124285635
SN - 0003-2700
VL - 94
SP - 2794
EP - 2802
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 6
ER -