1. Construction of 5-Fluorouracil and Gallium Corrole Conjugates for Enhanced Photodynamic Therapy.
- Author
-
Cen JH, Xie QH, Guo GH, Xu SY, Liu ZY, Liao YH, Zhong XP, and Liu HY
- Subjects
- Humans, Animals, Mice, Hep G2 Cells, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis, Mice, Inbred BALB C, Mice, Nude, Photochemotherapy, Fluorouracil pharmacology, Fluorouracil chemistry, Fluorouracil therapeutic use, Gallium chemistry, Gallium pharmacology, Porphyrins pharmacology, Porphyrins chemistry, Porphyrins therapeutic use, Photosensitizing Agents pharmacology, Photosensitizing Agents chemistry, Photosensitizing Agents chemical synthesis, Photosensitizing Agents therapeutic use, Apoptosis drug effects
- Abstract
Molecular hybridization is a well-established strategy for developing new drugs. In the pursuit of promising photosensitizers (PSs) with enhanced photodynamic therapy (PDT) efficiency, a series of novel 5-fluorouracil (5FU) gallium corrole conjugates ( 1-Ga-4-Ga ) were designed and synthesized by hybridizing a chemotherapeutic drug and PSs. Their photodynamic antitumor activity was also evaluated. The most active complex ( 2-Ga ) possesses a low IC
50 value of 0.185 μM and a phototoxic index of 541 against HepG2 cells. Additionally, the 5FU-gallium corrole conjugate ( 2-Ga ) exhibited a synergistic increase in cytotoxicity under irradiation. Excitedly, treatment of HepG2 tumor-bearing mice with 2-Ga under irradiation could completely ablate tumors without harming normal tissues. 2-Ga -mediated PDT could disrupt mitochondrial function, cause cell cycle arrest in the sub-G1 phase, and activate the cell apoptosis pathway by upregulating the cleaved PARP expression and the Bax/Bcl-2 ratios. This work provides a useful strategy for the design of new corrole-based chemo-photodynamic therapy drugs.- Published
- 2024
- Full Text
- View/download PDF