Totally Caged Type I Pro-Photosensitizer for Oxygen-Independent Synergistic Phototherapy of Hypoxic Tumors.
Adv Sci (Weinh)
; 11(31): e2400462, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38885361
ABSTRACT
Activatable type I photosensitizers are an effective way to overcome the insufficiency and imprecision of photodynamic therapy in the treatment of hypoxic tumors, however, the incompletely inhibited photoactivity of pro-photosensitizer and the limited oxidative phototoxicity of post-photosensitizer are major limitations. It is still a great challenge to address these issues using a single and facile design. Herein, a series of totally caged type I pro-photosensitizers (Pro-I-PSs) are rationally developed that are only activated in tumor hypoxic environment and combine two oxygen-independent therapeutic mechanisms under single-pulse laser irradiation to enhance the phototherapeutic efficacy. Specifically, five benzophenothiazine-based dyes modified with different nitroaromatic groups, BPN 1-5, are designed and explored as latent hypoxia-activatable Pro-I-PSs. By comparing their optical responses to nitroreductase (NTR), it is identified that the 2-methoxy-4-nitrophenyl decorated dye (BPN 2) is the optimal Pro-I-PSs, which can achieve NTR-activated background-free fluorescence/photoacoustic dual-modality tumor imaging. Furthermore, upon activation, BPN 2 can simultaneously produce an oxygen-independent photoacoustic cavitation effect and a photodynamic type I process at single-pulse laser irradiation. Detailed studies in vitro and in vivo indicated that BPN 2 can effectively induce cancer cell apoptosis through synergistic effects. This study provides promising potential for overcoming the pitfalls of hypoxic-tumor photodynamic therapy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Photosensitizing Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
Adv Sci (Weinh)
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Germany