Mild Acidosis-Directed Signal Amplification in Tumor Microenvironment via Spatioselective Recruitment of DNA Amplifiers
Dr. Zhenghan Di
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190 China
College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorProf. Dr. Xueguang Lu
Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 China
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
Search for more papers by this authorDr. Jian Zhao
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190 China
College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorProf. Ana Jaklenec
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
Search for more papers by this authorProf. Yuliang Zhao
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190 China
Search for more papers by this authorProf. Robert Langer
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
Search for more papers by this authorCorresponding Author
Prof. Lele Li
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190 China
College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorDr. Zhenghan Di
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190 China
College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorProf. Dr. Xueguang Lu
Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 China
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
Search for more papers by this authorDr. Jian Zhao
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190 China
College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorProf. Ana Jaklenec
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
Search for more papers by this authorProf. Yuliang Zhao
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190 China
Search for more papers by this authorProf. Robert Langer
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
Search for more papers by this authorCorresponding Author
Prof. Lele Li
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190 China
College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorGraphical Abstract
A DNA-based strategy is developed for spatially-selective amplification of acidic signals in the extracellular milieu of tumors. Amplified imaging of the tumor microenvironment with improved sensitivity was achieved by acidity-responsive engineering of the cell surface with DNA receptors for controlled recruitment of fluorescent amplifiers.
Abstract
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.
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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