Translation durch Konvergenz: Drug‐Delivery‐Forschung in multidisziplinären Teams

Traverso, Giovanni; Kirtane, Ameya R.; Schoellhammer, Carl M.; Langer, Robert

doi:10.1002/ange.201712512

Angewandte Chemie

2018

DOI: 10.1002/ange.201712512

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Translation durch Konvergenz: Drug‐Delivery‐Forschung in multidisziplinären Teams

Giovanni Traverso

Ameya R. Kirtane

Carl M. Schoellhammer³

et al.

Abstract: Die Kluft zwischen Wirkstoffentwicklung und der erfolgreichen Umsetzung in die klinische Praxis (Translation) ist gewaltig. Wirksame Lösungen erfordern die Zusammenarbeit multidisziplinärer Teams von unterschiedlicher Expertise (Konvergenz). Dieser Essay stellt zwei Fallbeispiele für die Entwicklung dauerhafter Wirkstoffverabreichungssysteme für Antimalaria‐ und antiretrovirale Medikamente im Magen‐Darm‐Trakt vor.

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Cited by 2 publications

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Targeted Singlet Oxygen Delivery: A Bioorthogonal Metabolic Shunt Linking Hypoxia to Fast Singlet Oxygen Release

Wang

et al. 2022

Angewandte Chemie

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Singlet oxygen can be generated by thermal cycloreversion of aromatic endoperoxides. However, for any practical potential of chemically generated singlet oxygen within a therapeutic context, the time and place of the release of this cytotoxic species must be tightly regulated. We now show that using a bimodular design with a hypoxia responsive unit and fluoride‐triggered endoperoxide unit, a bioorthogonal metabolic shunt can be established, where an enzymatically generated submicromolar fluoride signal plays a crucial role. Thus, cellular nitroreductase is repurposed in a bioorthogonal enzymatic activity, where it releases fluoride ions upon the reduction of a targeted compound. The fluoride ions released in the initial reaction remove the silyl stopper, yielding a highly accelerated release of singlet oxygen. The result is a remarkable difference in cytotoxicity between hypoxic and normoxic conditions as evidenced by microscopy, viability assays and the use of control compounds.

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Targeted Singlet Oxygen Delivery: A Bioorthogonal Metabolic Shunt Linking Hypoxia to Fast Singlet Oxygen Release

Wang

et al. 2022

Angewandte Chemie

View full text Add to dashboard Cite

show abstract

Targeted Singlet Oxygen Delivery: A Bioorthogonal Metabolic Shunt Linking Hypoxia to Fast Singlet Oxygen Release

Wang

et al. 2022

Angew Chem Int Ed

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Translation durch Konvergenz: Drug‐Delivery‐Forschung in multidisziplinären Teams

Cited by 2 publications

References 40 publications

Targeted Singlet Oxygen Delivery: A Bioorthogonal Metabolic Shunt Linking Hypoxia to Fast Singlet Oxygen Release

Targeted Singlet Oxygen Delivery: A Bioorthogonal Metabolic Shunt Linking Hypoxia to Fast Singlet Oxygen Release

Targeted Singlet Oxygen Delivery: A Bioorthogonal Metabolic Shunt Linking Hypoxia to Fast Singlet Oxygen Release

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