Rare Earth Nanocomposites Induced Autophagy For Photothermal Theranostics Of Cancer

Photothermal therapy（PTT）as a new method for tumor diagnosis and treatment can provide new avenues for precision medicine due to its low invasiveness,high efficiency,and precise spatial selectivity.The thermal produced during photothermal therapy can induce pro-survival autophagy to resist therapeutic pressure,reducing the effect of PTT.Manipulating autophagic processes have emerged as a promising strategy for synergizing nanomaterial-mediated PTT.Inhibition of the heat generated from the photothermal process-induced pro-survival autophagy can enhance nanomaterial-mediated PTT.However,as a unique inducer of autophagy,the autophagy induced by nanomaterials is often ignored.If the induced autophagy by the nanomaterial is pro-death,which is the opposite to the pro-survival autophagy induced by the heat,the dominant effect of the two needs to be weighed to maximize the tumor-suppressive effect.However,pro-survival and pro-death diminishes each partner under this circumstance.Therefore,it is of great significance to obtain nano-composites that can not only meet the requirements of image-guided photothermal therapy,but also induce pro-survival autophagy.The main research contents of this paper are as follows:（1）NaYF₄:Er,Yb,Nd@NaNdF₄ down conversion nanomaterials were synthesized by high temperature thermal decomposition.Pickling nanomaterials changed from oil phase to water phase,and a carbon shell as a photothermal agent was coated on the surface by hydrothermal method.PEI and FA were modified by covalent bonding to improve their biocompatibility and tumor targeting.The resulting nanocomposite（DCPF）not only has strong spectral emission in the near infrared region,but also has excellent photothermal conversion ability,and the ability to actively target tumor cells.（2）DCPF nanoparticles can induce autophagy after entering cells,and induce a complete autophagy process.By monitoring the in vitro experiments,DCPF nanoparticles induce pro-survival autophagy,which is consistent with the direction of heat-induced autophagy during PTT.This indicates that by coating carbon shells and FA on NaYF₄:Er,Yb@NaNdF₄ surfaces,not only image-guided photothermal therapy can be realized,but also the pro-death autophagy induced by down-conversion nanomaterials can be transformed into pro-survival autophagy.（3）By inhibition of autophagy can significantly improve the in vitro antitumor effect.Based on in vitro experiments,we conducted in vivo experiments to achieve image-guided photothermal therapy,and inhibition of autophagy can significantly improve the therapeutic effect of solid tumors.（3）The nanoparticle can be treated in vivo only if its biosafety is relatively good.Therefore,the toxicity of DCPF nanoparticles was monitored in vivo for 60 days,and the low toxicity and good biocompatibility of DCPF nanoparticles were confirmed by histological,hematological and oxidative stress analysis.