Selective in vivo metabolic cell-labeling-mediated cancer targeting
Hua Wang,Ruibo Wang,Kaimin Cai,Hua He,Yang Liu,Jonathan Yen,Zhiyu Wang,Ming Xu,Yiwen Sun,Xin Zhou,Qian Yin,Li Tang,Iwona T. Dobrucki,Lawrence W. Dobrucki,Eric J. Chaney,Stephen A. Boppart,Timothy M. Fan,Stéphane Lezmi,Xuesi Chen,Lichen Yin,Jianjun Cheng +20 more
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TLDR
This work inhibits the cell-labeling activity of tetraacetyl-N-azidoacetylmannosamine (Ac4ManAz) by converting its anomeric acetyl group to a caged ether bond that can be selectively cleaved by cancer-overexpressed enzymes and thus enables the overexpression of azido groups on the surface of cancer cells.Abstract:
Distinguishing cancer cells from normal cells through surface receptors is vital for cancer diagnosis and targeted therapy. Metabolic glycoengineering of unnatural sugars provides a powerful tool to manually introduce chemical receptors onto the cell surface; however, cancer-selective labeling still remains a great challenge. Herein we report the design of sugars that can selectively label cancer cells both in vitro and in vivo. Specifically, we inhibit the cell-labeling activity of tetraacetyl-N-azidoacetylmannosamine (Ac4ManAz) by converting its anomeric acetyl group to a caged ether bond that can be selectively cleaved by cancer-overexpressed enzymes and thus enables the overexpression of azido groups on the surface of cancer cells. Histone deacetylase and cathepsin L-responsive acetylated azidomannosamine, one such enzymatically activatable Ac4ManAz analog developed, mediated cancer-selective labeling in vivo, which enhanced tumor accumulation of a dibenzocyclooctyne-doxorubicin conjugate via click chemistry and enabled targeted therapy against LS174T colon cancer, MDA-MB-231 triple-negative breast cancer and 4T1 metastatic breast cancer in mice.read more
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Biomedical applications of copper-free click chemistry: in vitro , in vivo , and ex vivo
Eunha Kim,Heebeom Koo +1 more
TL;DR: Copper-free click chemistry has resulted in a change of paradigm, showing that artificial chemical reactions can occur on cell surfaces, in cell cytosol, or within the body.
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Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy.
TL;DR: Dextran nanoparticles loaded with a chemotherapeutic agent and bound to phages that eliminate a pro-tumoural gut bacterium and promote the growth of anticancer-compound-producing bacteria boost chemotherapy responses in mouse models of colorectal cancer.
Journal ArticleDOI
Practical Considerations, Challenges, and Limitations of Bioconjugation via Azide–Alkyne Cycloaddition
TL;DR: This focused review highlights practical approaches to AAC reactions for the synthesis of peptide or protein bioconjugates and contrasts current challenges and limitations in light of recent advances in the field.
Journal ArticleDOI
S-glycosylation-based cysteine profiling reveals regulation of glycolysis by itaconate.
Wei Qin,Ke Qin,Y. Zhang,Wentong Jia,Ying Chen,Bo Cheng,Linghang Peng,Nan Chen,Yuan Liu,Wen Zhou,Yan-Ling Wang,Xing Chen,Chu Wang +12 more
TL;DR: This study developed a specific thiol-reactive probe, 1-OH-Az, for quantitative chemoproteomic profiling of cysteine modifications by itaconate, and provided a global portrait of its proteome reactivity, finding that itaconates covalently modifies key glycolytic enzymes and impairs gly colytic flux mainly through inhibition of fructose-bisphosphate aldolase A (ALDOA).
Journal ArticleDOI
A Light-Up Probe with Aggregation-Induced Emission for Real-Time Bio-orthogonal Tumor Labeling and Image-Guided Photodynamic Therapy.
TL;DR: The first light-up probe based on a fluorogen with aggregation-induced emission for in vivo bio-orthogonal fluorescence turn-on tumor labeling is presented, showing negligible non-specific interaction with normal tissues.
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