TY - JOUR
T1 - Mild Acidosis-Directed Signal Amplification in Tumor Microenvironment via Spatioselective Recruitment of DNA Amplifiers
AU - Di, Zhenghan
AU - Lu, Xueguang
AU - Zhao, Jian
AU - Jaklenec, Ana
AU - Zhao, Yuliang
AU - Langer, Robert
AU - Li, Lele
N1 - Funding Information:
This research was supported financially by National Natural Science Foundation of China (22125402, 32101156), the Strategic Priority Research Program of Chinese Academy of Sciences (XDB36000000).
Publisher Copyright:
© 2022 Wiley-VCH GmbH.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - DNA biotechnology offers intriguing opportunities for amplification-based sensitive detection. However, spatiotemporally-controlled manipulation of signal amplification for in situ imaging of the tumor microenvironment remains an outstanding challenge. Here, we demonstrate a DNA-based strategy that can spatial-selectively amplify the acidic signal in the extracellular milieu of the tumor to achieve specific imaging with improved sensitivity. The strategy, termed mild acidosis-targeted amplification (MAT-amp), leverages the specific acidic microenvironment to engineer tumor cells with artificial DNA receptors through a pH (low) insertion peptide, which permits controlled recruitment of fluorescent amplifiers via a hybridization chain reaction. The acidosis-responsive amplification cascade enables significant fluorescence enhancement in tumors with a reduced background signal in normal tissues, leading to improved signal-to-background ratio. These results highlight the utility of MAT-amp for in situ imaging of the microenvironment characterized by pH disequilibrium.
AB - DNA biotechnology offers intriguing opportunities for amplification-based sensitive detection. However, spatiotemporally-controlled manipulation of signal amplification for in situ imaging of the tumor microenvironment remains an outstanding challenge. Here, we demonstrate a DNA-based strategy that can spatial-selectively amplify the acidic signal in the extracellular milieu of the tumor to achieve specific imaging with improved sensitivity. The strategy, termed mild acidosis-targeted amplification (MAT-amp), leverages the specific acidic microenvironment to engineer tumor cells with artificial DNA receptors through a pH (low) insertion peptide, which permits controlled recruitment of fluorescent amplifiers via a hybridization chain reaction. The acidosis-responsive amplification cascade enables significant fluorescence enhancement in tumors with a reduced background signal in normal tissues, leading to improved signal-to-background ratio. These results highlight the utility of MAT-amp for in situ imaging of the microenvironment characterized by pH disequilibrium.
KW - Cell Surface Engineering
KW - DNA Receptors
KW - Mild Acidosis
KW - Signal Amplification
KW - Tumor Microenvironment
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U2 - 10.1002/anie.202205436
DO - 10.1002/anie.202205436
M3 - Article
C2 - 35652128
AN - SCOPUS:85132163737
SN - 1433-7851
VL - 61
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 31
M1 - e202205436
ER -