Red light-activatable transition metal complexes have recently emerged as viable materials for use in photodynamic/photochemotherapeutic applications.Ideal photosensitizers or photochemotherapeutic agents are still an...Red light-activatable transition metal complexes have recently emerged as viable materials for use in photodynamic/photochemotherapeutic applications.Ideal photosensitizers or photochemotherapeutic agents are still an elusive goal.Herein,we report the synthesis,characterization and remarkable photodynamic activity of the[LaⅢ(Cur)2(L1)(NO3)](1)-functionalized gold nanocomposite,1-AuNPs,where Cur represents curcumin and L1 represents 5-(1,2-dithiolan-3-yl)-N-(1,10-phenanthroline-5-yl)pentanamide.Functionalization of complex 1 to gold nanoparticles led to a remarkable red shift(λ_(max),755 nm)in the surface plasmon resonance(SPR)band,making the La(Ⅲ)–curcumin-functionalized nanocomposite(1-AuNPs)an ideal photo-sensitizer for use in photodynamic applications.Several photophysical assays confirmed its high efficacy in generating singlet oxygen[ϕ(1O2),0.69]through a type-II photo-process.TD-DFT calculations also predicted the presence of a low-lying triplet excited state and efficient intersystem crossing for the nanoconjugate.The log P values along with the high binding affinity of the 1-AuNPs to serum albumin predicted cellular permeability and transportation through blood.Flowcytometric analysis indicated the selective accumulation and retention of 1-AuNPs in adenocarcinomic human alveolar basal epithelial cells(A549)compared with normal alveolar fibroblast cells(WI-38).Confocal microscopy confirmed the localization of the nanocomposite in mitochondria.The nanoconjugate,1-AuNPs,exhibited remarkable photodynamic activity against adenocarcinomic human alveolar basal epithelial cells(A549)(IC50:25μg mL^(-1) in light;>500μg mL^(-1) in dark)and immortalized human keratinocytes(HaCaT)(IC50:34μg mL^(-1) in light;>500μgmL^(-1) in dark)under red light(600–720 nm,30 J cm^(-2)),with remarkable photo-indices(PI>20).Red light-induced generation of 1O2 by 1-AuNPs in vitro was found to be primarily responsible for the upsetting of the mitochondrial membrane potential(MMP),which led to caspase-3 activated apoptosis in A549 cells via an intrinsic pathway.During apoptosis,the pro-apoptotic BAX protein was upregulated,while the antiapoptotic Bcl-2 protein was downregulated and responsible for apoptosis after the A549 cells were treated with the red light activated nanoconjugate(1-AuNPs).Overall,the La(Ⅲ)–curcumin-functionalized gold nanocomposite is an ideal next generation La(Ⅲ)-based photosensitizer for use in photodynamic applications.展开更多
基金the Board of Research in Nuclear Science(BRNS),Mumbai(37(2)/14/18/2017-BRNS)for financial support,and NIT Manipur for providing infrastructureWe sincerely thank Prof.Akhil R.Chakravarty,IISc Bangalore,for providing the facility used for cellular studies.We thank the Advanced Material Research Centre,IIT Mandi for recording NMR,ESI-MS,EDX,ICP-OES spectra,and TEM analysis and Miss V.V.Gandhi,BARC for FACS analysis.
文摘Red light-activatable transition metal complexes have recently emerged as viable materials for use in photodynamic/photochemotherapeutic applications.Ideal photosensitizers or photochemotherapeutic agents are still an elusive goal.Herein,we report the synthesis,characterization and remarkable photodynamic activity of the[LaⅢ(Cur)2(L1)(NO3)](1)-functionalized gold nanocomposite,1-AuNPs,where Cur represents curcumin and L1 represents 5-(1,2-dithiolan-3-yl)-N-(1,10-phenanthroline-5-yl)pentanamide.Functionalization of complex 1 to gold nanoparticles led to a remarkable red shift(λ_(max),755 nm)in the surface plasmon resonance(SPR)band,making the La(Ⅲ)–curcumin-functionalized nanocomposite(1-AuNPs)an ideal photo-sensitizer for use in photodynamic applications.Several photophysical assays confirmed its high efficacy in generating singlet oxygen[ϕ(1O2),0.69]through a type-II photo-process.TD-DFT calculations also predicted the presence of a low-lying triplet excited state and efficient intersystem crossing for the nanoconjugate.The log P values along with the high binding affinity of the 1-AuNPs to serum albumin predicted cellular permeability and transportation through blood.Flowcytometric analysis indicated the selective accumulation and retention of 1-AuNPs in adenocarcinomic human alveolar basal epithelial cells(A549)compared with normal alveolar fibroblast cells(WI-38).Confocal microscopy confirmed the localization of the nanocomposite in mitochondria.The nanoconjugate,1-AuNPs,exhibited remarkable photodynamic activity against adenocarcinomic human alveolar basal epithelial cells(A549)(IC50:25μg mL^(-1) in light;>500μg mL^(-1) in dark)and immortalized human keratinocytes(HaCaT)(IC50:34μg mL^(-1) in light;>500μgmL^(-1) in dark)under red light(600–720 nm,30 J cm^(-2)),with remarkable photo-indices(PI>20).Red light-induced generation of 1O2 by 1-AuNPs in vitro was found to be primarily responsible for the upsetting of the mitochondrial membrane potential(MMP),which led to caspase-3 activated apoptosis in A549 cells via an intrinsic pathway.During apoptosis,the pro-apoptotic BAX protein was upregulated,while the antiapoptotic Bcl-2 protein was downregulated and responsible for apoptosis after the A549 cells were treated with the red light activated nanoconjugate(1-AuNPs).Overall,the La(Ⅲ)–curcumin-functionalized gold nanocomposite is an ideal next generation La(Ⅲ)-based photosensitizer for use in photodynamic applications.
