TY - JOUR
T1 - A nanoparticle-based strategy for the imaging of a broad range of tumours by nonlinear amplification of microenvironment signals
AU - Wang, Yiguang
AU - Zhou, Kejin
AU - Huang, Gang
AU - Hensley, Christopher
AU - Huang, Xiaonan
AU - Ma, Xinpeng
AU - Zhao, Tian
AU - Sumer, Baran D.
AU - Deberardinis, Ralph J.
AU - Gao, Jinming
N1 - Funding Information:
This work is supported by the NIH (R01EB013149 and R01CA129011) and Cancer Prevention and Research Institute of Texas (RP120094). Animal imaging work is supported by the UT Southwestern Small Animal Imaging Resource Grant (U24 CA126608) and Simmons Cancer Center Support Grant (P30 CA142543). We thank H. Zhou for help with the Maestro imaging, X. Luo for assistance with animal handling, and J. T. Hsieh and L. Gandee for help with histology.
PY - 2014/2
Y1 - 2014/2
N2 - Stimuli-responsive nanomaterials are increasingly important in a variety of applications such as biosensing, molecular imaging, drug delivery and tissue engineering. For cancer detection, a paramount challenge still exists in the search for methods that can illuminate tumours universally regardless of their genotypes and phenotypes. Here we capitalized on the acidic, angiogenic tumour microenvironment to achieve the detection of tumour tissues in a wide variety of mouse cancer models. This was accomplished using ultra pH-sensitive fluorescent nanoprobes that have tunable, exponential fluorescence activation on encountering subtle, physiologically relevant pH transitions. These nanoprobes were silent in the circulation, and then strongly activated (>300-fold) in response to the neovasculature or to the low extracellular pH in tumours. Thus, we have established non-toxic, fluorescent nanoreporters that can nonlinearly amplify tumour microenvironmental signals, permitting the identification of tumour tissue independently of histological type or driver mutation, and detection of acute treatment responses much more rapidly than conventional imaging approaches.
AB - Stimuli-responsive nanomaterials are increasingly important in a variety of applications such as biosensing, molecular imaging, drug delivery and tissue engineering. For cancer detection, a paramount challenge still exists in the search for methods that can illuminate tumours universally regardless of their genotypes and phenotypes. Here we capitalized on the acidic, angiogenic tumour microenvironment to achieve the detection of tumour tissues in a wide variety of mouse cancer models. This was accomplished using ultra pH-sensitive fluorescent nanoprobes that have tunable, exponential fluorescence activation on encountering subtle, physiologically relevant pH transitions. These nanoprobes were silent in the circulation, and then strongly activated (>300-fold) in response to the neovasculature or to the low extracellular pH in tumours. Thus, we have established non-toxic, fluorescent nanoreporters that can nonlinearly amplify tumour microenvironmental signals, permitting the identification of tumour tissue independently of histological type or driver mutation, and detection of acute treatment responses much more rapidly than conventional imaging approaches.
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U2 - 10.1038/nmat3819
DO - 10.1038/nmat3819
M3 - Article
C2 - 24317187
AN - SCOPUS:84892980829
SN - 1476-1122
VL - 13
SP - 204
EP - 212
JO - Nature Materials
JF - Nature Materials
IS - 2
ER -