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fDevelopment of Self-Activated Photosensitizers based on the Chemiluminescent System of Marine Coelenterazine.

Authors :
da Silva, Luís Pinto
Magalhães, Carla M.
González-Berdullas, Patricia
da Silva, Joaquim C.G. Esteves
Source :
Photodiagnosis & Photodynamic Therapy; Apr2024, Vol. 46, pN.PAG-N.PAG, 1p
Publication Year :
2024

Abstract

Photodynamic therapy (PDT) of cancer possesses advantageous features, such as a minimally invasive nature and few side-effect [1]. However, its use can be restricted to more surface tumors, due to its dependance on light-irradiation. To overcome this problem, we propose the development of single-molecule photosensitizers (PSs), based on chemiluminescent (CL) marine Coelenterazine (Clz) [2-6], which can be self-activated in the absence of light. Clz analogs were synthesized via routes optimized by our team [2-6], and their structure was characterized by HR-MS, NMR and FTIR spectroscopy. They were subjected to a through luminometric and photophysical characterization, to determine their CL features and singlet oxygen sensitization [2-6]. Their toxicity was investigated in vitro toward different cancer (breast, prostate, neuroblastoma, lung and gastric) and noncancer (breast and keratinocytes) cell lines, via the MTT assay in the absence of light [2-6]. The obtained Clz analogs were designed so their CL reaction generate mainly triplet states, instead of singlet excited ones [2-6]. They were shown to indeed be able to sensitize the highly cytotoxic singlet oxygen, without light-irradiation, due to a CL reaction triggered solely by molecule overexpressed in cancer cells (superoxide anion) [2-6]. In vitro assays showed that these analogs present cytotoxicity toward all the different studied cancer cell lines [2-6]. Moreover, some of them even showed comparable or even better activity than a reference chemotherapeutic drug [3,4]. Finally, a promising profile of safety was observed in testing with noncancer cells [3]. Different single-molecule PSs were developed, which are capable of intracellular self-activation without light-irradiation [2-6]. Namely, they are directly chemiexcited to triplet excited states via a CL reaction triggered by a molecule overexpressed in cancer cells, which generates singlet oxygen without light-irradiation. This new approach was found to induce toxicity toward different cancer cell lines, while possessing a promising profile of safety for noncancer cells. Thus, these PSs can provide a pathway for eliminating the light-related restrictions of PDT, while maintaining its advantages. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15721000
Volume :
46
Database :
Supplemental Index
Journal :
Photodiagnosis & Photodynamic Therapy
Publication Type :
Academic Journal
Accession number :
177515388
Full Text :
https://doi.org/10.1016/j.pdpdt.2024.104129