TY - JOUR
T1 - Nitroreductase-Induced Aggregation of Gold Nanoparticles for "Off-On" Photoacoustic Imaging of Tumor Hypoxia
AU - Li, Xin
AU - Fang, Xueyang
AU - Li, Shiying
AU - Lui, Kwok Ho
AU - Lo, Wai Sum
AU - Gu, Yanjuan
AU - Wong, Wing Tak
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Hypoxia is an important phenomenon due to insufficient oxygen supply in tumor tissue, and nitroreductase (NTR) is a characteristic enzyme used for evaluating hypoxia level in tumors. In this work, we designed a smart gold nanoparticle (AuNPs), modified by 16-mercaptoundecanoic acid (MHDA) and hypoxia-responsive 11-(2-nitro-1H-imidazol-1-yl)undecane-1-thiol (NI) ligand, that responds to the hypoxic environment in tumor sites. With proper surface ligand composition, the responsive nanoprobe exhibited aggregation through the bioreduction of the nitro group on NI ligands under hypoxic conditions and the UV-vis absorption peak maximum would shift to 630 nm from 530 nm, which acts as an "off-on" contrast agent for tumor hypoxic photoacoustic (PA) imaging. In vitro and in vivo experiments revealed that AuNPs@MHDA/NO₂ exhibited an enhanced PA signal in hypoxic conditions. This study demonstrates the potential of hypoxia-responsive AuNPs as novel and sensitive diagnostic agents, which lays a firm foundation for precise cancer treatment in the future.
AB - Hypoxia is an important phenomenon due to insufficient oxygen supply in tumor tissue, and nitroreductase (NTR) is a characteristic enzyme used for evaluating hypoxia level in tumors. In this work, we designed a smart gold nanoparticle (AuNPs), modified by 16-mercaptoundecanoic acid (MHDA) and hypoxia-responsive 11-(2-nitro-1H-imidazol-1-yl)undecane-1-thiol (NI) ligand, that responds to the hypoxic environment in tumor sites. With proper surface ligand composition, the responsive nanoprobe exhibited aggregation through the bioreduction of the nitro group on NI ligands under hypoxic conditions and the UV-vis absorption peak maximum would shift to 630 nm from 530 nm, which acts as an "off-on" contrast agent for tumor hypoxic photoacoustic (PA) imaging. In vitro and in vivo experiments revealed that AuNPs@MHDA/NO₂ exhibited an enhanced PA signal in hypoxic conditions. This study demonstrates the potential of hypoxia-responsive AuNPs as novel and sensitive diagnostic agents, which lays a firm foundation for precise cancer treatment in the future.
UR - http://www.scopus.com/inward/record.url?scp=85122773608&partnerID=8YFLogxK
U2 - 10.1166/jbn.2021.3195
DO - 10.1166/jbn.2021.3195
M3 - Journal article
C2 - 34906279
AN - SCOPUS:85122773608
SN - 1550-7033
VL - 17
SP - 2186
EP - 2197
JO - Journal of Biomedical Nanotechnology
JF - Journal of Biomedical Nanotechnology
IS - 11
ER -
