Responsive Degradable Theranostic Agents Enable Controlled Selenium Delivery to Enhance Photothermal Radiotherapy and Reduce Side Effects

Abstract Radiotherapy (RT) is a popular clinical therapy method for extending cancer patient survival, but is hampered by severe side effects and the weak therapy effect. Herein, responsive degradable selenium (Se) theranostic agents (Se@SiO 2 @Bi nanocomposites (NCs)) are fabricated, which combine computed tomography (CT) imaging and simultaneously enhance the therapeutic effects of photothermal therapy (PTT) and RT, while reducing the side effects of radiation. The Se@SiO 2 @Bi theranostic agents can accumulate at the tumor site, and responsively decompose to releease Se, avoiding systemic toxicity by the element. Se enhances the effect of PTT/RT, simultaneously reducing the side effects of RT. The Se@SiO 2 @Bi NCs as CT agents also exhibit significantly enhanced contrast imaging performance due to the high atomic number of Bi. More importantly, the Se@SiO 2 @Bi NCs can be rapidly excreted without long‐term toxicity, owing to responsive degradation into ultrasmall particles (<5 nm) at the tumor site. In vitro and in vivo results show that the Se@SiO 2 @Bi NCs can remarkably inhibit tumor cells, without causing appreciable toxicity during the treatment. This study opens a new perspective in rationally designing responsive degradable theranostic agents for future tumor therapy with enhanced therapeutic efficacy and lesser side effects.