Abstract
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.
Highlights
In addition to surgery and chemotherapy, radiotherapy is an important treatment in cancer therapy that is suitable for breast,[1,2] cervical,[3] lung[4,5,6] and brain[7,8] cancers
The high-resolution transmission electron microscopy image presented in Figure 1c shows hexagonal lattice fringes with 0.21 nm spacing corresponding to the (110) plane of the Bi2Se3 crystal.[48]
In the Bi2Se3-CS-RGD NS treatment, no dark spots could be detected in the hepatic sinusoid, verifying its selectivity. These results show that covalent conjugation of RGD improves Bi2Se3 NS accumulation in tumor tissues and reduces the in vivo toxicity, making Bi2Se3-CS-RGD NSs safe in cancer radiotherapy
Summary
In addition to surgery and chemotherapy, radiotherapy is an important treatment in cancer therapy that is suitable for breast,[1,2] cervical,[3] lung[4,5,6] and brain[7,8] cancers. Radiotherapy fails to fully eradicate tumors due to inevitable damage to surrounding healthy tissues and the radiation insensitivity of some tumors. Various chemical radiosensitizers have been suggested to accentuate the effects of radiation therapy. ‘electronaffinic’ nitroaromatic compounds as hypoxic-specific cytotoxins,[9,10] and pyrimidines substituted with bromine or iodine can be incorporated into DNA to enhance free radical damage.[11] Morever, it has been reported that pentoxifylline can improve tumor oxygenation and radiation responses.[12] few radiosensitizers are available on the market due to the difficulty and high cost of large-scale production; development of new radiotherapy agents is of scientific and clinical interest
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