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 Bi₂Se₃nanosheets (NSs) as a radiosensitizer. Chitosan (CS) and RGD peptide are employed to enhance the radiotherapy efficiencyand biocompatibility. The Bi₂Se₃-CS-RGD NSs exhibit excellent targeting ability to αvβ3 integrin-overexpressing cancer cells andpotent radiosensitization efficiency with high stability. Detailed in vitro experiments show that the Bi₂Se₃-CS-RGD NSs enhancethe sensitivity of HeLa cells to X-ray-induced cell death by inhibiting TrxR activities and activating downstream reactive oxygenspecies-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 enablesthe 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 efficientlyexpelled from the body after 48 h post injection. This study reveals an effective and safe theranostic agent for next-generationcancer radiotherapy.