Structure-Guided Design and Synthesis of a Mitochondria-Targeting Near-Infrared Fluorophore with Multimodal Therapeutic Activities
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 29(2017), 43 vom: 05. Nov. |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2017
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| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article cancer theranostics heptamethine cyanine dyes mitochondria-targeting agents near-infrared imaging phototherapy Fluorescent Dyes Indocyanine Green IX6J1063HV |
| Zusammenfassung: | © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. An urgent challenge for imaging-guided disease-targeted multimodal therapy is to develop the appropriate multifunctional agents to meet the requirements for potential applications. Here, a rigid cyclohexenyl substitution in the middle of a polymethine linker and two asymmetrical amphipathic N-alkyl side chains to indocyanine green (ICG) (the only FDA-approved NIR contrast agent) are introduced, and a new analog, IR-DBI, is developed with simultaneous cancer-cell mitochondrial targeting, NIR imaging, and chemo-/PDT/PTT/multimodal therapeutic activities. The asymmetrical and amphipathic structural modification renders IR-DBI a close binding to albumin protein site II to form a drug-protein complex and primarily facilitates its preferential accumulation at tumor sites via the enhanced permeability and retention (EPR) effect. The released IR-DBI dye is further actively taken up by cancer cells through organic-anion-transporting polypeptide transporters, and the lipophilic cationic property leads to its selective accumulation in the mitochondria of cancer cells. Finally, based on the high albumin-binding affinity, IR-DBI is modified into human serum albumin (HSA) via self-assembly to produce a nanosized complex, which exhibits significant improvement in the cancer targeting and multimodal cancer treatment with better biocompatibility. This finding may present a practicable strategy to develop small-molecule-based cancer theranostic agents for simultaneous cancer diagnostics and therapeutics |
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| Beschreibung: | Date Completed 17.01.2019 Date Revised 30.03.2022 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.201704196 |