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Learning from Artemisinin: Bioinspired Design of a Reaction-Based Fluorescent Probe for the Selective Sensing of Labile Heme in Complex Biosystems SCIE
期刊论文 | 2020 , 142 (5) , 2129-2133 | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
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Abstract :

Labile heme (LH) is an important signaling molecule in virtually all organisms. However, specifically detecting LH remains an outstanding challenge. Herein, by learning from the bioactivation mechanism of artemisinin, we have developed the first LH-responsive small-molecule fluorescent probe, HNG, based on a 4-amino-1,8-naphthalimide (NG) fluorophore. HNG showed high selectivity for LH without interference from hemin, protein-interacting heme, and zinc protoporphyrin. Using HNG, the changes of LH levels in live cells were imaged, and a positive correlation of LH level with the degree of hemolysis was uncovered in hemolytic mice. Our study not only presents the first molecular probe for specific LH detection but also provides a strategy to construct probes with high specificity through a bioinspired approach.

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GB/T 7714 Xu, Shuai , Liu, Hong-Wen , Chen, Lanlan et al. Learning from Artemisinin: Bioinspired Design of a Reaction-Based Fluorescent Probe for the Selective Sensing of Labile Heme in Complex Biosystems [J]. | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 2020 , 142 (5) : 2129-2133 .
MLA Xu, Shuai et al. "Learning from Artemisinin: Bioinspired Design of a Reaction-Based Fluorescent Probe for the Selective Sensing of Labile Heme in Complex Biosystems" . | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 142 . 5 (2020) : 2129-2133 .
APA Xu, Shuai , Liu, Hong-Wen , Chen, Lanlan , Yuan, Jie , Liu, Yongchao , Teng, Lili et al. Learning from Artemisinin: Bioinspired Design of a Reaction-Based Fluorescent Probe for the Selective Sensing of Labile Heme in Complex Biosystems . | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 2020 , 142 (5) , 2129-2133 .
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Learning from Artemisinin: Bioinspired Design of a Reaction-Based Fluorescent Probe for the Selective Sensing of Labile Heme in Complex Biosystems Scopus
期刊论文 | 2020 , 142 (5) , 2129-2133 | Journal of the American Chemical Society
Learning from Artemisinin: Bioinspired Design of a Reaction-Based Fluorescent Probe for the Selective Sensing of Labile Heme in Complex Biosystems EI
期刊论文 | 2020 , 142 (5) , 2129-2133 | Journal of the American Chemical Society
Tumor-acidity activated surface charge conversion of two-photon fluorescent nanoprobe for enhanced cellular uptake and targeted imaging of intracellular hydrogen peroxide SCIE
期刊论文 | 2019 , 10 (40) , 9351-9357 | CHEMICAL SCIENCE
WoS CC Cited Count: 29
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Abstract :

Elevated levels of intracellular hydrogen peroxide (H2O2) are closely related to the development of cancers. Specific imaging of H2O2 in tumor sites would be significant not only for cancer diagnosis but also for gaining a deep understanding of the role of H2O2 in cancer. However, traditional fluorescent probes based only on responses to overexpression levels of H2O2 in cancer cells are insufficient to distinguish cancer cells from other unhealthy or healthy cells in complex biological systems. Herein, we developed a smart, two-photon fluorescent GC-NABP nanoprobe with pH-dependent surface charge conversion for tumor-targeted imaging of H2O2. The nanoprobe was constructed by the self-assembly of amphiphilic GC-NABP, which was synthesized by grafting the hydrophobic, H2O2-responsive and two-photon fluorophore, NABP, onto hydrophilic biopolymer glycol chitosan (GC). Taking advantage of pH-titratable amino groups on GC, the nanoprobe had the capability of surface charge conversion from negative at physiologic pH to positive in the acidic tumor microenvironment. The positive charge of the nanoprobe promoted electrostatic interactions with cell membranes, leading to enhanced cellular uptake in acidic environment. Upon cellular uptake, the high level of H2O2 in tumor cells triggered boronate deprotections of the nanoprobe, generating a "turn-on" fluorescence emission for H2O2 imaging. The nanoprobe exhibited good sensitivity and selectivity to H2O2 with a detection limit down to 110 nM in vitro. The results from flow cytometry and two-photon fluorescence imaging of H2O2 in living cells and tissues evidenced the enhanced cellular uptake and targeted imaging of intracellular H2O2 in acidic environment. Compared to control nanoparticles that lack pH sensitivity, our nanoprobe showed enhanced accumulation in tumor sites and was applied to targeted imaging of H2O2 in a tumor-bearing mouse model. This work demonstrates that the nanoprobe GC-NABP holds great promise for tumor-specific imaging of cellular H2O2, providing a potential tool to explore the role of H2O2 in tumor sites.

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GB/T 7714 Chen, Lanlan , Xu, Shuai , Li, Wei et al. Tumor-acidity activated surface charge conversion of two-photon fluorescent nanoprobe for enhanced cellular uptake and targeted imaging of intracellular hydrogen peroxide [J]. | CHEMICAL SCIENCE , 2019 , 10 (40) : 9351-9357 .
MLA Chen, Lanlan et al. "Tumor-acidity activated surface charge conversion of two-photon fluorescent nanoprobe for enhanced cellular uptake and targeted imaging of intracellular hydrogen peroxide" . | CHEMICAL SCIENCE 10 . 40 (2019) : 9351-9357 .
APA Chen, Lanlan , Xu, Shuai , Li, Wei , Ren, Tianbing , Yuan, Lin , Zhang, Shusheng et al. Tumor-acidity activated surface charge conversion of two-photon fluorescent nanoprobe for enhanced cellular uptake and targeted imaging of intracellular hydrogen peroxide . | CHEMICAL SCIENCE , 2019 , 10 (40) , 9351-9357 .
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Tumor-acidity activated surface charge conversion of two-photon fluorescent nanoprobe for enhanced cellular uptake and targeted imaging of intracellular hydrogen peroxide EI
期刊论文 | 2019 , 10 (40) , 9351-9357 | Chemical Science
Tumor-acidity activated surface charge conversion of two-photon fluorescent nanoprobe for enhanced cellular uptake and targeted imaging of intracellular hydrogen peroxide Scopus
期刊论文 | 2019 , 10 (40) , 9351-9357 | Chemical Science
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