Photodynamic therapy(PDT)has received much attention in recent years.However,traditional photosensitizers(PSs)applied in PDT usually suffer from aggregation-caused quenching(ACQ)effect in H_(2)O,single and inefficient...Photodynamic therapy(PDT)has received much attention in recent years.However,traditional photosensitizers(PSs)applied in PDT usually suffer from aggregation-caused quenching(ACQ)effect in H_(2)O,single and inefficient photochemical mechanism of action(MoA),poor cancer targeting ability,etc.In this work,two novel Ru(II)-based aggregation-induced emission(AIE)agents(Ru1 and Ru2)were developed.Both complexes exhibited long triplet excited lifetimes and nearly 100%singlet oxygen quantum yields in H_(2)O.In addition,Ru1 and Ru2 displayed potent photo-catalytic reduced nicotinamide adenine dinucleotide(NADH)oxidation activity with turnover frequency(TOF)values of about 1779 and 2000 h^(−1),respectively.Therefore,both Ru1 and Ru2 showed efficient PDT activity towards a series of cancer cells.Moreover,Ru2 was further loaded in bovine serum albumin(BSA)to enhance the tumor targeting ability in vivo,and the obtained Ru2@BSA could selectively accumulate in tumor tissues and effectively inhibit tumor growth on a 4T1 tumor-bearing mouse model.So far as we know,this work represents the first report about Ru(Ⅱ)-)AIE agents that possess high singlet oxygen quantum yields and also potent photocatalytic NADH oxidation activity,and may provide new ideas for rational design of novel PSs with efficient PDT activity.展开更多
Intracellular bacteria(ICB),cloaked by the protective barriers of host cells,pose a formidable challenge to selective and efficient eradication.The employment of activatable photosensitizers based antibacterial photod...Intracellular bacteria(ICB),cloaked by the protective barriers of host cells,pose a formidable challenge to selective and efficient eradication.The employment of activatable photosensitizers based antibacterial photodynamic therapy(a PDT)holds significant potential for selective imaging and photo-inactivation of ICB while minimizing side effects on normal cells.Drawing inspiration from the elevated hypochlorous acid(HClO)levels in ICB infected phagocytes,herein we firstly designed and synthesized a series of HCl Oresponsive dinuclear Ru(Ⅱ)complexes(Ru1-Ru3)to achieve such a goal.Initially,the luminescence,^(1)O_(2)generation and a PDT activity of these Ru(Ⅱ)complexes were suppressed due to the quenching effect of the azo group,but were recovered after reaction with HCl O in solutions or within ICB infected phagocytes.The detailed results revealed that Ru1 and Ru3 could not only selectively visualize ICB,but also demonstrated remarkable a PDT activity against ICB,surpassing vancomycin both in vitro and in vivo.展开更多
Photo-catalytic oxidation of intracellular nicotinamide adenine dinucleotide(2'-phosphate)(NAD(P)H)has attracted much attention for cancer therapy.However,the general oxygen-dependent mechanism heavily depresses t...Photo-catalytic oxidation of intracellular nicotinamide adenine dinucleotide(2'-phosphate)(NAD(P)H)has attracted much attention for cancer therapy.However,the general oxygen-dependent mechanism heavily depresses the efficacy in hypoxic tumors.To solve this problem,herein platinum nanoparticles(Pt NPs)with catalase-like(CAT-like)and catalytic H_(2)evolution activities were introduced as a powerful assistant to enhance the photo-catalytic NAD(P)H oxidation of Ru1([Ru(phen)2(PIP-OCH_(3))]^(2+),phen=1,10-phenanthroline,PIP-OCH_(3)=2-(4-methoxy phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline)under hypoxic and even oxygen-free conditions.Firstly,Pt NPs can transform the original and in situ formed H_(2)O_(2)once again into O_(2)by the CAT-like activity,thus relieving tumor hypoxia and realizing cyclic utilization(at least in part)of the precious oxygen in hypoxia.Secondly,Pt NPs can also be served as H_(2)evolution catalysts while using Ru1 as the photosensitizer and NAD(P)H as the electron and proton donor.In this process,NAD(P)H is oxidized without the participation of oxygen,which can provide an effective way even under oxygen-free conditions.Via co-encapsulation of Rul and Pt NPs in bovine serum albumin(BSA)with tumor targeting ability,the resultant Ru/Pt@BSA could photo-catalyze intracellular NAD(P)H oxidation under hypoxic conditions(3%O_(2)),and exhibited an efficient and selective anticancer activity both in vitro and in vivo.Our results may provide new sights for efficient and targeted cancer treatment underhypoxic conditions.展开更多
基金supported by National Natural Science Foundation of China(NSFC,No.22371289).
文摘Photodynamic therapy(PDT)has received much attention in recent years.However,traditional photosensitizers(PSs)applied in PDT usually suffer from aggregation-caused quenching(ACQ)effect in H_(2)O,single and inefficient photochemical mechanism of action(MoA),poor cancer targeting ability,etc.In this work,two novel Ru(II)-based aggregation-induced emission(AIE)agents(Ru1 and Ru2)were developed.Both complexes exhibited long triplet excited lifetimes and nearly 100%singlet oxygen quantum yields in H_(2)O.In addition,Ru1 and Ru2 displayed potent photo-catalytic reduced nicotinamide adenine dinucleotide(NADH)oxidation activity with turnover frequency(TOF)values of about 1779 and 2000 h^(−1),respectively.Therefore,both Ru1 and Ru2 showed efficient PDT activity towards a series of cancer cells.Moreover,Ru2 was further loaded in bovine serum albumin(BSA)to enhance the tumor targeting ability in vivo,and the obtained Ru2@BSA could selectively accumulate in tumor tissues and effectively inhibit tumor growth on a 4T1 tumor-bearing mouse model.So far as we know,this work represents the first report about Ru(Ⅱ)-)AIE agents that possess high singlet oxygen quantum yields and also potent photocatalytic NADH oxidation activity,and may provide new ideas for rational design of novel PSs with efficient PDT activity.
基金supported by National Natural Science Foundation of China(No.22371289)。
文摘Intracellular bacteria(ICB),cloaked by the protective barriers of host cells,pose a formidable challenge to selective and efficient eradication.The employment of activatable photosensitizers based antibacterial photodynamic therapy(a PDT)holds significant potential for selective imaging and photo-inactivation of ICB while minimizing side effects on normal cells.Drawing inspiration from the elevated hypochlorous acid(HClO)levels in ICB infected phagocytes,herein we firstly designed and synthesized a series of HCl Oresponsive dinuclear Ru(Ⅱ)complexes(Ru1-Ru3)to achieve such a goal.Initially,the luminescence,^(1)O_(2)generation and a PDT activity of these Ru(Ⅱ)complexes were suppressed due to the quenching effect of the azo group,but were recovered after reaction with HCl O in solutions or within ICB infected phagocytes.The detailed results revealed that Ru1 and Ru3 could not only selectively visualize ICB,but also demonstrated remarkable a PDT activity against ICB,surpassing vancomycin both in vitro and in vivo.
基金financially supported by Research Equipment Development Project of Chinese Academy of Sciences(No.YJKYYQ20210014).
文摘Photo-catalytic oxidation of intracellular nicotinamide adenine dinucleotide(2'-phosphate)(NAD(P)H)has attracted much attention for cancer therapy.However,the general oxygen-dependent mechanism heavily depresses the efficacy in hypoxic tumors.To solve this problem,herein platinum nanoparticles(Pt NPs)with catalase-like(CAT-like)and catalytic H_(2)evolution activities were introduced as a powerful assistant to enhance the photo-catalytic NAD(P)H oxidation of Ru1([Ru(phen)2(PIP-OCH_(3))]^(2+),phen=1,10-phenanthroline,PIP-OCH_(3)=2-(4-methoxy phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline)under hypoxic and even oxygen-free conditions.Firstly,Pt NPs can transform the original and in situ formed H_(2)O_(2)once again into O_(2)by the CAT-like activity,thus relieving tumor hypoxia and realizing cyclic utilization(at least in part)of the precious oxygen in hypoxia.Secondly,Pt NPs can also be served as H_(2)evolution catalysts while using Ru1 as the photosensitizer and NAD(P)H as the electron and proton donor.In this process,NAD(P)H is oxidized without the participation of oxygen,which can provide an effective way even under oxygen-free conditions.Via co-encapsulation of Rul and Pt NPs in bovine serum albumin(BSA)with tumor targeting ability,the resultant Ru/Pt@BSA could photo-catalyze intracellular NAD(P)H oxidation under hypoxic conditions(3%O_(2)),and exhibited an efficient and selective anticancer activity both in vitro and in vivo.Our results may provide new sights for efficient and targeted cancer treatment underhypoxic conditions.
