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Red light triggered photodynamic-chemo combination therapy using a prodrug caged by photosensitizer.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2021 Apr 05; Vol. 215, pp. 113251. Date of Electronic Publication: 2021 Feb 12. - Publication Year :
- 2021
-
Abstract
- Development of the drug with high therapeutic efficacy and low toxicity is crucial to cancer ablation. In this study, we have demonstrated a red light-responsive prodrug BDP-TK-CPT by connecting the chemotherapeutic agent camptothecin with a boron dipyrromethene (BDP)-based photosensitizer via a reactive oxygen species (ROS)-labile thioketal chain. Since camptothecin is modified by a BDP-based macrocycle at the active site, the formed prodrug displays an extremely low toxicity in dark. However, upon illumination by red light, it can efficiently generate ROS leading to cell death by photodynamic therapy. Meanwhile, the ROS generated can destroy thioketal group to release free camptothecin which further results in local cell death by chemotherapy. The combined antitumor effects of the prodrug have been verified in HepG2, EC109, and HeLa cancer cells and mice bearing H22 tumors. This study may provide an alternative strategy for stimuli-responsive combination treatment of tumors by conjugation of ROS-activatable prodrugs with photosensitizing agents.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents chemical synthesis
Antineoplastic Agents radiation effects
Apoptosis drug effects
Cell Line, Tumor
Combined Modality Therapy
Drug Therapy
Female
Humans
Light
Mice
Necrosis chemically induced
Photochemotherapy
Photosensitizing Agents chemical synthesis
Photosensitizing Agents radiation effects
Prodrugs chemical synthesis
Prodrugs radiation effects
Reactive Oxygen Species metabolism
Antineoplastic Agents therapeutic use
Neoplasms drug therapy
Photosensitizing Agents therapeutic use
Prodrugs therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 215
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33611187
- Full Text :
- https://doi.org/10.1016/j.ejmech.2021.113251