Abstract
The interaction between ionizing radiation and materials composed of high Z-number elements could be applied to enhance radiotherapy. In this work, we fabricated an ionizing radiation-sensitive nanoplatform by grafting chlorin e6 (Ce6) onto the surface of ultrasmall gold nanoparticles (Au NPs), aiming to enhance the radiation effects induced by different radiation sources. Poly-(ethylene glycol) (PEG) was applied as the shape-controlling agent during the synthesis of Au nanoparticles. The as-prepared Au NPs show excellent monodispersity, with an average hydrodynamic diameter of around 5 nm. U87 and HeLa cell lines were utilized to evaluate the biological properties of the as-prepared Ce6-Au NPs. The Cell Counting Kit-8 (CCK-8) results reveal that the Ce6-Au NPs conjugate can significantly affect the growth of U87 cells under X-ray and (68)Ga exposure, which is not seen for the pure Au NPs, Ce6, and physically mixed Ce6 and Au NPs. Moreover, the Ce6-Au NPs conjugate show evident cell prefoliation inhibition of U87 and HeLa cells under both X-ray and (18)F-radiolabeled fluorodeoxyglucose ((18)F-FDG) exposure. These results indicate that interaction exists between Ce6 and Au NPs under radiation exposure. The mRNA sequencing results show that the tumor killing performance induced by Ce6-Au NPs may be due to regulation of the tumor microenvironment (TME) and immune-relevant signaling pathway. Our research proves that the rational combination of Au NPs and Ce6 can make better use of ionizing radiation energy and thus improve the therapeutic outcome of radiotherapy.