Inhibition of Pro‐Survival Autophagy Induced by Rare‐Earth Nanocomposites for Promoting Photothermal Therapy of Visualized Tumors

Abstract Manipulation of autophagic processes has emerged as a promising strategy for synergizing nanoagent‐mediated photothermal therapy (PTT). Most of the current studies focus on improving PTT efficacy by inhibiting pro‐survival autophagy induced by the heat generated from the photothermal process. However, autophagy induced by the nanoagents is usually ignored, which may weaken the effect of autophagy‐mediated efficacy improvement in PTT if induced autophagy is pro‐death. Therefore, this work aims at developing a nanoagent that is able to induce heat‐synergetic pro‐survival autophagy to optimize the efficacy of PTT. An approach is developed to coat carbon layer, polyethylenimine (PEI), and folic acid (FA) on NaYF4:Er,Yb,Nd@NaNdF4 (DCNPs@C@PEI@FA, DCPF) nanoparticles successively, giving access to the nanoagent to induce pro‐survival autophagy. The synthetic imaging‐guided photothermal nanoagent displays outstanding targeting ability and biocompatibility based on the surface modification of PEI and FA. By using an autophagy inhibitor chloroquine, a conspicuously synergistic effect on DCPF‐mediated PTT in vitro and in vivo tumor models (HeLa) is achieved. A promising strategy is presented here to enhance the efficacy of imaging‐guided PTT by modulating the autophagy induced by the nanoagent.