TY - JOUR
T1 - Study of copper-cysteamine based X-ray induced photodynamic therapy and its effects on cancer cell proliferation and migration in a clinical mimic setting
AU - Chen, Xiangyu
AU - Liu, Jiayi
AU - Li, Ya
AU - Pandey, Nil Kanatha
AU - Chen, Taili
AU - Wang, Lingyun
AU - Amador, Eric Horacio
AU - Chen, Weijun
AU - Liu, Feiyue
AU - Xiao, Enhua
AU - Chen, Wei
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2022/1
Y1 - 2022/1
N2 - Copper-cysteamine as a new generation of sensitizers can be activated by light, X-rays, microwaves, or ultrasound to produce reactive oxygen species. X-ray induced photodynamic therapy (X-PDT) has been studied extensively; however, most of the studies reported so far were conducted in the laboratory, which is not conducive to the clinical translation conditions. In this contribution, for the first time, we investigated the treatment efficiency of copper-cysteamine (Cu-Cy) based X-PDT by mimicking the clinical conditions with a clinical linear accelerator and building deep-seated tumor models to study not only the effectiveness but also its effects on the cell migration and proliferation in the level of the cell, tissue, and animal. The results showed that, without X-ray irradiation, Cu-Cy nanoparticles (NPs) had a low toxicity in HepG2, SK-HEP-1, Li-7, and 4T1 cells at a concentration below 100 mg/L. Interestingly, for the first time, it was observed that Cu-Cy mediated X-PDT can inhibit the proliferation and migration of these cell lines in a dose-dependent manner. Antigen markers of migration and cell proliferation, proliferating cell nuclear antigen (PCNA) and E-cadherin, from tumor tissue in the X-PDT group were remarkably different from that of the control group. Furthermore, the MRI assessment showed that the Cu-Cy based X-PDT inhibited the growth of deeply located tumors in mice and rabbits (p < 0.05) without any obvious toxicities in vivo. Overall, these new findings demonstrate that Cu-Cy NPs have a safe and promising clinical application prospect in X-PDT to improve the efficiency of radiotherapy (RT) for deep-seated tumors and effectively inhibit tumor cell proliferation and migration.
AB - Copper-cysteamine as a new generation of sensitizers can be activated by light, X-rays, microwaves, or ultrasound to produce reactive oxygen species. X-ray induced photodynamic therapy (X-PDT) has been studied extensively; however, most of the studies reported so far were conducted in the laboratory, which is not conducive to the clinical translation conditions. In this contribution, for the first time, we investigated the treatment efficiency of copper-cysteamine (Cu-Cy) based X-PDT by mimicking the clinical conditions with a clinical linear accelerator and building deep-seated tumor models to study not only the effectiveness but also its effects on the cell migration and proliferation in the level of the cell, tissue, and animal. The results showed that, without X-ray irradiation, Cu-Cy nanoparticles (NPs) had a low toxicity in HepG2, SK-HEP-1, Li-7, and 4T1 cells at a concentration below 100 mg/L. Interestingly, for the first time, it was observed that Cu-Cy mediated X-PDT can inhibit the proliferation and migration of these cell lines in a dose-dependent manner. Antigen markers of migration and cell proliferation, proliferating cell nuclear antigen (PCNA) and E-cadherin, from tumor tissue in the X-PDT group were remarkably different from that of the control group. Furthermore, the MRI assessment showed that the Cu-Cy based X-PDT inhibited the growth of deeply located tumors in mice and rabbits (p < 0.05) without any obvious toxicities in vivo. Overall, these new findings demonstrate that Cu-Cy NPs have a safe and promising clinical application prospect in X-PDT to improve the efficiency of radiotherapy (RT) for deep-seated tumors and effectively inhibit tumor cell proliferation and migration.
KW - Cell migration
KW - Copper-cysteamine
KW - Nanoparticle
KW - Photodynamic therapy
KW - Proliferation
KW - X-ray
UR - http://www.scopus.com/inward/record.url?scp=85106944048&partnerID=8YFLogxK
U2 - 10.1016/j.bioactmat.2021.05.016
DO - 10.1016/j.bioactmat.2021.05.016
M3 - Article
AN - SCOPUS:85106944048
SN - 2452-199X
VL - 7
SP - 504
EP - 514
JO - Bioactive Materials
JF - Bioactive Materials
ER -
