Improvement in Photodynamic Activity of Gallium Hydroxycorrole Towards Hepatocellular Cancer Cells invitro and invivo

doi:10.19894/j.issn.1000-0518.230339

Chinese Journal of Applied Chemistry ›› 2024, Vol. 41 ›› Issue (8): 1184-1192.DOI: 10.19894/j.issn.1000-0518.230339

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Improvement in Photodynamic Activity of Gallium Hydroxycorrole Towards Hepatocellular Cancer Cells invitro and invivo

Yong-Hui ZHONG¹, Xiao-Qian OU², Yue-Qing HUANG², Pei-Sha ZHENG², Hui-Lin HUANG², Jia-Qi ZHENG², Lei SHI²(), Zhao ZHANG³()

^1.Department of Laboratory Medicine Foshan Forth People's Hospital，Foshan 528041，China
^2.Department of Chemistry and Materials Science，Guangdong University of Education，Guangzhou 510800，China
^3.Department of Biochemistry and Molecular Biology，Guangdong Medical University，Zhanjiang 524023，China

Received:2023-10-30 Accepted:2024-06-17 Published:2024-08-01 Online:2024-08-27
Contact: Lei SHI,Zhao ZHANG
Supported by:
the Youth Project of National Natural Science Foundation of China(82003786);the Basic and Applied Basic Research Foundation Project of Guangdong Science and Technology Department(2019A1515110338);the Construction of High-level Hospital of Foshan Fourth People's Hospital(FSYKF-2020012);the Quality and Reform Project of Guangdong Province Undergraduate Teaching

Abstract

Abstract:

10-（4- hydroxyphenyl）-5， 15-bis（pentafluorophenyl） corrole （1） and its metal gallium complex （1-Ga） were prepared， and the photodynamic activity of hepatocellular carcinoma cells was studied by molecular biotechnology. The results indicated that the phototoxicity of corroles depended largely on the central metal， and gallium could enhance the photodynamic activities. In liver cancer cells， 1-Ga triggered the significant production of reactive oxygen species （ROS） and the change of mitochondrial membrane potential under light irradiation， which eventually led to cancer cell necrosis and apoptosis. The half inhibitory concentration of 1-Ga on the photodynamic activity of human hepatoma cells （MHCC97H） and human hepatoma cells （HepG2） is between 2~4 μmol/L， while the concentration of 1 is greater than 4 μmol/L. These corroles showed high biocompatibility and photodynamic anticancer efficiency， which were obvious in mouse cancer model. Compared with the control group， the mass of tumor tissue in the treatment group decreased by more than 70%. And the mechanism may be related to the influence of ROS production on mitochondrial function. It is worth mentioning that the photodynamic activity of 1-Ga is obviously better than that of 1， which may be related to the photodynamic production of more ROS by gallium corrole.

Key words: Photodynamic activity, Corrole, Gallium, Liver cancer

CLC Number:

O614.3

Yong-Hui ZHONG, Xiao-Qian OU, Yue-Qing HUANG, Pei-Sha ZHENG, Hui-Lin HUANG, Jia-Qi ZHENG, Lei SHI, Zhao ZHANG. Improvement in Photodynamic Activity of Gallium Hydroxycorrole Towards Hepatocellular Cancer Cells invitro and invivo[J]. Chinese Journal of Applied Chemistry, 2024, 41(8): 1184-1192.

Figures/Tables 8

Fig.1 The synthetic route of 1 and 1-Ga

Fig.2 UV-Vis spectra of 1 and 1-Ga （A， B）；FL spectra of 1 and 1-Ga （C） and the fluorescence attenuation profile of 1 and 1-Ga （D） at the peak wavelength of fluorescence （○， experimental curve； ---， fitting curve）； The solvent is toluene， the test concentration is 5 μmol/L， and the excitation wavelength of fluorescence is 405 nm

Fig.3 Cytotoxic effects of 1 （A） and 1-Ga （B） on human hepatocel lular cancer cell lines with/without illumination. Optical images of MHCC97H cells after incubation with 1-Ga for 24 h in different concentration （C）. Red arrows represent the apoptotic cells. The rulers are all 100 μm

Fig.4 Cell localization of 1-Ga （2.0 μmol/L） in MHCC97H cells determined by fluorescence microscopy. Nuclei： Hoechst-33342 stain（blue）. The rulers are all 100 μm. Complex represents the field of view of the red fluorescent channel

Fig.5 Effect of 1-Ga （2.0 μmol/L） on the MMP decrease in MHCC97H cells. MHCC97H cells were treated with 1-Ga for 24 h， and stained with the fluorescent probe JC-1. （Control） Representative images from three independent experiments are shown. （1-Ga） Quantitative analysis of the fluorescence intensity of JC-1 monomers or aggregates. **P＜0.01， *P＜0.05， n=3. The rulers are all 100 μm

Fig.6 Intracellular ROS detection in MHCC97H cells after treatment with 1-Ga （2.0 μmol/L）， which determined by fluorescence microscopy （The rulers are all 100 μm）

Fig.7 The study of cell motility and metastasis by wound healing assay and transwell assay. （A） A wound healing assay was used to evaluate the migration of MHCC97H after silencing by 1-Ga. （B） The effects of metastasis in MHCC97H cells after treatment with 1-Ga. The rulers are all 100 μm

Fig.8 The photodynamic anti-tumor effect of 1-Ga in MHCC97H xenograft tumors. （A） Representative tumor images at 24 days post-PDT treatment. （B） The weight of the tumors for each group at the end of the observation period. （C） The body mass of mice from each group at the end of the observation period. Data are presented as the mean ± SEM. ** represents P＜0.01， * represents P＜0.05， n=3. （D） The histology analysis by H&E for the mice tumor after 1 and 1-Ga PDT treatment. Red arrows represent the apoptotic cells. The rulers are all 100 μm

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Improvement in Photodynamic Activity of Gallium Hydroxycorrole Towards Hepatocellular Cancer Cells invitro and invivo

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