Decorated ultrathin bismuth selenide nanosheets as targeted theranostic agents for in vivo imaging guided cancer radiation therapy

An efficient radiotherapeutic agent is synthesized using ultrathin two-dimensional 30-nm-wide and 2-nm-thick Bi2Se3 nanosheets (NSs) as a radiosensitizer. Chitosan (CS) and RGD peptide are employed to enhance the radiotherapy efficiency and biocompatibility. The Bi2Se3-CS-RGD NSs exhibit excellent targeting ability to αvβ3 integrin-overexpressing cancer cells and potent radiosensitization efficiency with high stability. Detailed in vitro experiments show that the Bi2Se3-CS-RGD NSs enhance the sensitivity of HeLa cells to X-ray-induced cell death by inhibiting TrxR activities and activating downstream reactive oxygen species-mediated signaling pathways. In vivo experiments using intravenous or intratumor injection demonstrate that the Bi2Se3-CS-RGD NSs are more efficient tumor growth inhibitors compared to bare Bi2Se3 NSs. The multifunctionality of the NSs enables the use of photoacoustic imaging and magnetic resonance imaging to examine their targeting ability and therapeutic effects, respectively. In addition, the RGD-decorated Bi2Se3 NSs show much better in vivo biocompatibility and can be efficiently expelled from the body after 48 h post injection. This study reveals an effective and safe theranostic agent for next-generation cancer radiotherapy. A nanomaterial that enhances the targeted destruction of cancer cells by radiotherapy has been demonstrated by scientists in China. Radiotherapy uses X-rays to destroy cancerous cells, but some cancers are not sensitive to X-rays. Injecting an agent into the body that binds to cancer cells can make them more sensitive, but it is difficult to make such agents on large scales. Tianfeng Chen from Jinan University in Guangzhou and co-workers combined two-dimensional sheets of bismuth selenide with chitosan and a peptide to create a biocompatible material that enhances radiotherapy efficiency. The material shows excellent ability to target cancer cells and has a potent radiosensitization efficiency with high stability. Furthermore, it has good biocompatibility and is efficiently expelled from the body efficiently after injection. Ultrathin Bi2Se3-CS-RGD NSs with excellent tumor-targeting ability and potent radiosensitization efficiency are constructed for imaging-guided cancer radiotherapy. The NSs in combination with X-ray irradiation inhibit HeLa cell growth by inducing G0/G1 cycle arrest and mitochondria-mediated intrinsic cell apoptosis, inhibiting TrxR and activating downstream ROS-mediated signaling pathways. Moreover, RGD coating enables the NSs to aggregate in the tumor regions quickly enabling efficient PAI of the entire tumor to facilitate radiotherapy of cervical cancer. Taken together, this study provides an effective and safe theranostic agent for next-generation cancer radiotherapy.