Dual Cathepsin B and Glutathione-Activated Dimeric and Trimeric Phthalocyanine-Based Photodynamic Molecular Beacons for Targeted Photodynamic Therapy
| Autor: | Dennis K. P. Ng, Roy C. H. Wong, Pui-Chi Lo, Ligang Yu, Wing-Ping Fong, Leo K. B. Tam |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_treatment
Antineoplastic Agents Photodynamic therapy Peptide Isoindoles Fluorescence Cathepsin B chemistry.chemical_compound Biopolymers Cell Line Tumor Drug Discovery medicine Humans Cathepsin chemistry.chemical_classification Photosensitizing Agents Chemistry Glutathione Photochemotherapy Phthalocyanine Biophysics Molecular Medicine Linker Intracellular |
| Zdroj: | Journal of Medicinal Chemistry. 64:17455-17467 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Two dual stimuli-activated photosensitizers were developed, in which two or three glutathione (GSH)-responsive 2,4-dinitrobenzenesulfonate (DNBS)-substituted zinc(II) phthalocyanine units were connected via one or two cathepsin B-cleavable Gly-Phe-Leu-Gly peptide linker(s). These dimeric and trimeric phthalocyanines were fully quenched in the native form due to the photoinduced electron transfer to the DNBS substituents and the self-quenching of the phthalocyanine units. In the presence of GSH and cathepsin B, or upon internalization into A549 and HepG2 cancer cells, these probes were activated through the release of free phthalocyanine units. The intracellular fluorescence intensity was increased upon post-incubation with GSH ester or reduced upon pre-treatment with a cathepsin B inhibitor. Upon light irradiation, these photosensitizers became highly cytotoxic with IC50 values of 0.21-0.39 μM. The photocytotoxicity was also dependent on the intracellular GSH and cathepsin B levels. The results showed that these conjugates could serve as smart photosensitizers for targeted photodynamic therapy. |
| Databáze: | OpenAIRE |
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