Cross-Linking of Thiolated Paclitaxel-Oligo(p-phenylene vinylene) Conjugates Aggregates inside Tumor Cells Leads to "Chemical Locks" That Increase Drug Efficacy
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 30(2018), 10 vom: 17. März |
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| Weitere Verfasser: | , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2018
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| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article antitumor assembly inside cells chemical locks drug resistance supramolecular paclitaxel Antineoplastic Agents Antineoplastic Agents, Phytogenic Micelles Polyvinyls mehr... |
| Zusammenfassung: | © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. How to reduce the resistance of certain tumor cells to paclitaxel (PTX) and related taxoid anticancer drugs is a major challenge for improving cure rates. An oligo(p-phenylenevinylene) unit with thiol groups and a PTX unit (OPV-S-PTX), which enhances drug efficacy and reverses resistance is thus designed. The mechanism involves diffusion of OPV-S-PTX into the cell, where π-π interactions lead to aggregation. Cross-linking of the aggregates via oxidation of thiol groups is favored in tumor cells because of the higher reactive oxygen species (ROS) concentration. Cross-linked aggregates "chemically lock" the multichromophore particle for a more persistent effect. The IC50 of OPV-S-PTX for tumor cell line A549 is reduced down to 0.33 × 10-9 m from that observed for PTX itself (41 × 10-9 m). Enhanced efficacy by OPV-S-PTX is proposed to proceed via acceleration of microtubule bundle formation. A549/T-inoculated xenograft mice experiments reveal suppression of tumor growth upon OPV-S-PTX treatment. Altogether, these results show that the internal cross-linking of OPV-S-PTX through ROS provides a means to discriminate between tumor and healthy cells and the formation of the chemically locked particles enhances drug efficacy and helps in reducing resistance |
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| Beschreibung: | Date Completed 07.03.2019 Date Revised 30.09.2020 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.201704888 |