Study of copper-cysteamine based X-ray induced photodynamic therapy and its effects on cancer cell proliferation and migration in a clinical mimic setting

Abstract

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.

Radionuclide Delivery Strategies in Tumor Treatment: A Systematic Review

“…The use of copper sulfide (CuS) nanoparticles, indeed, has been proved to enhance, in vitro, the photothermal ablation (PTA) of cervical cancer cells. [ 39 ] Copper–cysteamine nanoparticles (Cu–Cy), moreover, can be used—combined with X-rays—to make an effective photodynamic therapy (PDT), thus enhancing the penetration depths of light and solving the problem of hypoxia associated with some kind of tumors [ 40 , 41 , 42 , 43 , 44 ].…”

Colorectal liver metastasis: molecular mechanism and interventional therapy

“… 421 The most recent studies prove that this new Cu-Cy nanoparticle possess anti-tumoral effects and potential molecular mechanisms on B16 melanoma through X-PDT and X-ray induced antitumor immunity, 422 and most importantly is that X-PDT is exceptionally effective with clinical X-rays used for irradiation in clinic settings. 423 We believe that these new technologies could provide good solutions for CRC treatment.…”

Construction of Novel Nanocomposites (Cu-MOF/GOD@HA) for Chemodynamic Therapy

“…MTT experiments were used to evaluate the lethality of Cu-MOF, Cu-MOF/GOD and Cu-MOF/GOD@HA [37][38][39][40]. The viabilities of MCF-7 cells treated with Cu-MOF, Cu-MOF/GOD and Cu-MOF/GOD@HA at several concentrations (0, 10, 20, 30, 50, 70, 100 µg mL -1 ) levels were calculated, as illustrated in Figure 4A.…”