Phototriggered Secretion of Membrane Compartmentalized Bioactive Agents

• Published in: Angewandte Chemie 2016-12, Vol.128 (52), p.16314-16317
• Main Authors: Hughes, Robert M., Marvin, Christina M., Rodgers, Zachary L., Ding, Song, Oien, Nathan P., Smith, Weston J., Lawrence, David S.
• Format: Article
• Language: English
• Subjects: Biocompatibility; Chemistry; Cobalamine; Conjugates; Erythrocytes; Fluorescence; Illumination; Membranen; Membranes; Photolyse; Prodrugs; Secretions; Wavelengths; Wirkstofftransport
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201609731

A strategy for the light‐activated release of bioactive compounds (BODIPY, colchicine, paclitaxel, and methotrexate) from membrane‐enclosed depots is described. We have found that membrane‐permeable bioagents can be rendered membrane impermeable by covalent attachment to cobalamin (Cbl) through a photocleavable linker. These Cbl‐bioagent conjugates are imprisoned within lipid‐enclosed compartments in the dark, as exemplified by their retention in the interior of erythrocytes. Subsequent illumination drives the secretion of the bioactive species from red blood cells. Photorelease is triggered by wavelengths in the red, far‐red, and near‐IR regions, which can be pre‐assigned by affixing a fluorophore with the desired excitation wavelength to the Cbl‐bioagent conjugate. Pre‐assigned wavelengths allow different biologically active compounds to be specifically and unambiguously photoreleased from common carriers. Wirkstofftransport: Membranimpermeable, photoresponsive Konjugate wurden in membranäre Kompartimente eingefügt. Bestrahlung mit Licht erzeugt ein membranpermeables biologisch aktives Agens, das rasch sekretiert wird. Die Wellenlänge für die Photofreisetzung kann gezielt eingestellt werden, was die spezifische Freisetzung unterschiedlicher Bioagenzien aus einem gemeinsamen Träger ermöglicht.