Tianfeng Chen

Selenium‐Doped Nanoheterojunctions for Highly Efficient Cancer Radiosensitization

AbstractExploring efficient and low‐toxicity radiosensitizers to break through the bottleneck of radiation tolerance, immunosuppression and poor prognosis remains one of the critical developmental challenges in radiotherapy. Nanoheterojunctions, due to their unique physicochemical properties, have demonstrated excellent radiosensitization effects in radiation energy deposition and in lifting tumor radiotherapy inhibition. Herein, they doped selenium (Se) into prussian blue (PB) to construct a nano‐heterojunction (Se@PB), which could promote the increase of Fe2+/Fe3+ ratio and conversion of Se to a high valence state with Se introduction. The Fe2+‐Se‐Fe3+ electron transfer chain accelerates the rate of electron transfer on the surface of the nanoparticles, which in turn endows it with efficient X‐ray energy transfer and electron transport capability, and enhances radiotherapy physical sensitivity. Furthermore, Se@PB induces glutathione (GSH) depletion and Fe2+ accumulation through pro‐Fenton reaction, thereby disturbs the redox balance in tumor cells and enhances biochemical sensitivity of radiotherapy. As an excellent radiosensitizer, Se@PB effectively enhances X‐ray induced mitochondrial dysfunction and DNA damage, thereby promotes cell apoptosis and synergistic cervical cancer radiotherapy. This study elucidates the radiosensitization mechanism of Se‐doped nanoheterojunction from the perspective of the electron transfer chain and biochemistry reaction, which provides an efficient and low‐toxic strategy in radiotherapy.

Adjusting the lipid–water distribution coefficient of iridium(iii) complexes to enhance the cellular penetration and treatment efficacy to antagonize cisplatin resistance in cervical cancer

The effective design of metal complexes to manipulate their lipid–water distribution coefficient is an appealing strategy for improving their cellular penetration and treatment efficacy.

Stable high-oxidation-state complex in situ Mn(v)–Mn(iii) transition to achieve highly efficient cervical cancer therapy

Stable high-oxidation-state Mn complexes were employed for efficient cancer therapy through an in situ Mn(v)–Mn(iii) transition to disrupt the redox balance.

Selenium promotes immunogenic radiotherapy against cervical cancer metastasis through evoking P53 activation

Radiotherapy is still the recommended treatment for cervical cancer. However, radioresistance and radiation-induced side effects remain one of the biggest clinical problems. Selenium (Se) has been confirmed to exhibit radiation-enhancing effects for cancer treatment. However, Se species dominate the biological activities and which form of Se possesses better radiosensitizing properties and radiation safety remains elusive. Here, different Se species (the valence state of Se ranged from - 2, 0, +4 to + 6) synergy screen was carried out to identify the potential radiosensitizing effects and radiation safety of Se against cervical cancer. We found that the therapeutic effects varied with the changes in the Se valence state. Sodium selenite (+4) displayed strong cancer-killing effects but also possessed severe cytotoxicity. Sodium selenate (+6) neither enhanced the killing effects of X-ray nor possessed anticancer activity by its alone treatment. Although nano-selenium (0), especially Let-SeNPs, has better radiosensitizing activity, the - 2 organic Se, such as selenadiazole derivative SeD (-2) exhibited more potent anticancer effects and possessed a higher safe index. Overall, the selected Se drugs were able to synergize with X-ray to inhibit cell growth, clone formation, and cell migration by triggering G2/M phase arrest and apoptosis, and SeD (-2) was found to exhibit more potent enhancing capacity. Further mechanism studies showed that SeD mediated p53 pathway activation by inducing DNA damage through promoting ROS production. Additionally, SeD combined with X-ray therapy can induce an anti-tumor immune response in vivo. More importantly, SeD combined with X-ray significantly inhibited the liver metastasis of tumor cells and alleviated the side effects caused by radiation therapy in tumor-bearing mice. Taken together, this study demonstrates the radiosensitization and radiation safety effects of different Se species, which may shed light on the application of such Se-containing drugs serving as side effects-reducing agents for cervical cancer radiation treatment.

Selenium-containing metallodrug overcomes cervical cancer radioresistance through physical–chemical dual sensitization

Selenium-containing metallodrugs with enzyme-mimicking properties respond to X-ray to achieve radiotherapy sensitization.