ArticleNature chemistry2018
Enrichment-triggered prodrug activation demonstrated through mitochondria-targeted delivery of doxorubicin and carbon monoxide.
Article in Nature chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
85 citing papers in PubMed.
- Harnessing endogenous carbon monoxide for cancer-selective drug synthesis.Nature communications · 2026Article
- Red light-responsive bioorthogonal chemistry enabled on-demand prodrug activation for cancer therapy.Acta pharmaceutica Sinica. B · 2026Article
- A Metal-Free Carbon Monoxide Prodrug Suppresses Metastasis of Pancreatic and Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spatiotemporally controlled drug release via a click-release system utilizing mono-alkyl-hydroxylamine and cyclooctyne chemistry.Nature communications · 2026Article
- Biotin-mediated drug delivery: does the biotin transporter mediate uptake of biotin conjugates?Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Morpholine-Facilitated Enrichment-Triggered Delivery of Carbon Monoxide to Lysosome: A Feasibility Study.Chemical biology & drug design · 2025Article
- Organic Carbon Monoxide Prodrugs Activated by Endogenous Reactive Oxygen Species for Targeted Delivery.Journal of the American Chemical Society · 2025Article
- Mitigating Tumor Recurrence through Mitochondrial Metabolism Inhibition: A Novel NIR Laser-Induced Therapeutic Strategy.Biological procedures online · 2025Article
- In situ construction of intracellular supramolecular assemblies as an alternative strategy for protein degradation.Nature communications · 2025Article
- Click-Triggered Bioorthogonal Bond-Cleavage Reactions.Topics in current chemistry (Cham) · 2025Review
- Implantable bioelectronic devices for photoelectrochemical and electrochemical modulation of cells and tissues.Nature reviews bioengineering · 2025Article
- Carbon monoxide potentiates the effect of corticosteroids in suppressing inflammatory responses in cell culture.Bioorganic & medicinal chemistry · 2025Article
- Toward Realization of Bioorthogonal Chemistry in the Clinic.Topics in current chemistry (Cham) · 2025Review
- Exploring New Bioorthogonal Catalysts: Scaffold Diversity in Catalysis for Chemical Biology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Metal-organic framework-based smart stimuli-responsive drug delivery systems for cancer therapy: advances, challenges, and future perspectives.Journal of nanobiotechnology · 2025Review
- A Tale of Two Cities in Fluorescent Sensing of Carbon Monoxide: Probes That Detect CO and Those That Detect Only Chemically Reactive CO Donors (CORMs), but Not CO.The Journal of organic chemistry · 2024Review
- Sydnthiones are versatile bioorthogonal hydrogen sulfide donors.Nature communications · 2024Article
- Metal-Free CO Prodrugs Activated by Molecular Oxygen Protect against Doxorubicin-Induced Cardiomyopathy in Mice.Journal of medicinal chemistry · 2024Article
- CO prodrugs: A new scaffold of adamantane-fused norbornen-7-ones with tunable water solubility.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2024Article
- Advances in Immunomodulatory Mesoporous Silica Nanoparticles for Inflammatory and Cancer Therapies.Biomolecules · 2024Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Controlled activation is a critical component in prodrug development. Here we report a concentration-sensitive platform approach for bioorthogonal prodrug activation by taking advantage of reaction kinetics. Using two 'click and release' systems, we demonstrate enrichment and prodrug activation specifically in mitochondria to demonstrate the principle of the approach. In both cases, the payload (doxorubicin or carbon monoxide) was released inside the mitochondrial matrix following the enrichment-initiated click reaction. Furthermore, mitochondria-targeted delivery yielded substantial augmentation of functional biological and therapeutic effects in vitro and in vivo when compared to controls, which did not result in enrichment. This method is thus a platform for targeted drug delivery that is amenable to conjugation with a variety of molecules and is not limited to cell-surface delivery. Taken together, these two 'click and release' pairs clearly demonstrate the concept of enrichment-triggered drug release and the critical feasibility of treating clinically relevant diseases such as acute liver injury and cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.