Construction of 5‑Fluorouracil and Gallium Corrole Conjugates for Enhanced Photodynamic Therapy

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 IC50 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.