Cell-Mediated Assembly of Phototherapeutics

Light‐activatable drugs offer the promise of controlled release with exquisite temporal and spatial resolution. However, light‐sensitive prodrugs are typically converted to their active forms using short‐wavelength irradiation, which displays poor tissue penetrance. We report herein erythrocyte‐medi...

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Bibliographic Details
Published in:Angewandte Chemie 2014-10, Vol.126 (41), p.11125-11128
Main Authors: Smith, Weston J., Oien, Nathan P., Hughes, Robert M., Marvin, Christina M., Rodgers, Zachary L., Lee, Junghyun, Lawrence, David S.
Format: Article
Language:eng ; ger
Subjects:
Active control
Assembly
Chemical compounds
Chemistry
Cobalamine
Controlled release
Dihydrofolate reductase
Drug delivery systems
Drugs
Erythrocytes
Photochemie
Polymerization
Prodrugs
Wavelengths
Wirkstofftransport
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Summary:Light‐activatable drugs offer the promise of controlled release with exquisite temporal and spatial resolution. However, light‐sensitive prodrugs are typically converted to their active forms using short‐wavelength irradiation, which displays poor tissue penetrance. We report herein erythrocyte‐mediated assembly of long‐wavelength‐sensitive phototherapeutics. The activating wavelength of the constructs is readily preassigned by using fluorophores with the desired excitation wavelength λex. Drug release from the erythrocyte carrier was confirmed by standard analytical tools and by the expected biological consequences of the liberated drugs in cell culture: methotrexate, binding to intracellular dihydrofolate reductase; colchicine, inhibition of microtubule polymerization; dexamethasone, induced nuclear migration of the glucocorticoid receptor. Das optische Fenster des Gewebes wird von einer wellenlängenverschlüsselten Wirkstofftransportstrategie genutzt. Das photoresponsive System entsteht durch Aggregation eines Lipid‐Cobalamin‐Wirkstoff‐ und eines Lipid‐Fluorophor‐Konstrukts auf der Erythrozyten‐Oberfläche. Die Wellenlänge für die photolytische Cobalamin‐Wirkstoff‐Spaltung wird durch Verwendung einer entsprechenden Lipid‐Fluorophor‐„Antenne“ ausgewählt.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201406216