A multifunctional nanoplatform(USiCeCurAu)has been developed that integrates upconversion nanoparticles(UCNPs),gold nanoparticles(AuNPs),cerium oxide(CeO_(2)),and a thioketal-curcumin-triphenylphosphonium conjugate(TK...A multifunctional nanoplatform(USiCeCurAu)has been developed that integrates upconversion nanoparticles(UCNPs),gold nanoparticles(AuNPs),cerium oxide(CeO_(2)),and a thioketal-curcumin-triphenylphosphonium conjugate(TK-CUR-TPP)to enable synergistic tumor therapy via photodynamic(PDT),chemodynamic(CDT),and mild photothermal therapy(mPTT).In this strategy,AuNPs attached to the surface serve as a“pore locker”,cloaking CeO_(2)and CUR before entering tumor cells.UCNPs convert near-infrared(NIR)light into UV and visible light emission,simultaneously initiating AuNP aggregation via photoclick chemistry,CeO_(2)-mediated reactive oxygen species(ROS)generation,and TPP-CUR-driven PDT.The CeO_(2)amplifies oxidative stress by depleting glutathione(GSH)and catalyzing ROS production(O_(2)^(·-)and·OH),while releasing oxygen to relieve tumor hypoxia.The release of TPP-CUR not merely resumes the negativity of the surface,but also disrupts mitochondrial function and downregulates heat shock proteins(HSPs),further sensitizing tumor cells to mPTT(~45℃)performed by light-induced AuNP aggregation after detachment due to electrostatic repulsion.Importantly,ROS-scavenging ability post-PTT of CeO_(2)has been demonstrated to effectively mitigate excessive inflammation and prevent severe scab formation.This fully integrated,lightand ROS-responsive nanoplatform affords significant therapeutic efficacy in 4T1 tumor-bearing BALB/c mice,reducing tumor volume from 185 to 27 mm^(3)following a single tail-vein injection.展开更多
基金funded by Hong Kong Research Grant Council(GRF14300822)Faculty of Science of the Chinese University of Hong Kong(CRIMS)+1 种基金the Natural Science Foundation of Shandong Province(ZR2023MC178)Youth Innovation Team Development Project of Shandong Province(Food Nanotechnology innovation team).
文摘A multifunctional nanoplatform(USiCeCurAu)has been developed that integrates upconversion nanoparticles(UCNPs),gold nanoparticles(AuNPs),cerium oxide(CeO_(2)),and a thioketal-curcumin-triphenylphosphonium conjugate(TK-CUR-TPP)to enable synergistic tumor therapy via photodynamic(PDT),chemodynamic(CDT),and mild photothermal therapy(mPTT).In this strategy,AuNPs attached to the surface serve as a“pore locker”,cloaking CeO_(2)and CUR before entering tumor cells.UCNPs convert near-infrared(NIR)light into UV and visible light emission,simultaneously initiating AuNP aggregation via photoclick chemistry,CeO_(2)-mediated reactive oxygen species(ROS)generation,and TPP-CUR-driven PDT.The CeO_(2)amplifies oxidative stress by depleting glutathione(GSH)and catalyzing ROS production(O_(2)^(·-)and·OH),while releasing oxygen to relieve tumor hypoxia.The release of TPP-CUR not merely resumes the negativity of the surface,but also disrupts mitochondrial function and downregulates heat shock proteins(HSPs),further sensitizing tumor cells to mPTT(~45℃)performed by light-induced AuNP aggregation after detachment due to electrostatic repulsion.Importantly,ROS-scavenging ability post-PTT of CeO_(2)has been demonstrated to effectively mitigate excessive inflammation and prevent severe scab formation.This fully integrated,lightand ROS-responsive nanoplatform affords significant therapeutic efficacy in 4T1 tumor-bearing BALB/c mice,reducing tumor volume from 185 to 27 mm^(3)following a single tail-vein injection.
