Herein,we report on the successful encapsulation into human H-ferritin of two highly charged Ru(Ⅱ)polypyridyl complexes,[Ru(phen)2L’]^(2+)(Ru1,with L’=4,4’-(2,5,8,11,14-pentaaza[15])-2,2’-bipyridilophane)and[Ru(p...Herein,we report on the successful encapsulation into human H-ferritin of two highly charged Ru(Ⅱ)polypyridyl complexes,[Ru(phen)2L’]^(2+)(Ru1,with L’=4,4’-(2,5,8,11,14-pentaaza[15])-2,2’-bipyridilophane)and[Ru(phen)2L’’]^(2+)(Ru2,with L’’=4,4’-bis-[methylen-(1,4,7,10-tetraazacyclododecane)]-2,2’-bipyridine).The resulting Ru(Ⅱ)-ferritin nanocomposites are highly luminescent,display great stability in physiological conditions and preserve the native shell–core structure of the protein.Moreover,the singlet oxygen sensitizing properties of metal complexes,established by independent spectrophotometric and spectrofluorimetric measurements,are largely maintained also in their encapsulated form.Ru(Ⅱ)-ferritin nanocomposites are exclusively internalized by cancer cells expressing the transferrin receptor 1(TfR1)(i.e.HeLa and A2780 with respect to non-cancerous C2C12 myoblasts).Immunofluorescence analysis also reveals the co-localization of Ru1 and Ru2 with the TfR1 in the internal cellular compartments of HeLa and A2780 cells,highlighting the crucial role played by the receptor-mediated endocytosis of H-type ferritins exerted by TfR1.Finally,an MTT assay probed that light-activation effectively leads to a marked dose-dependent cytotoxic effect uniquely against cancer cells.This study underlines the potential of human H-ferritin as a valuable tool for the tumor-targeted delivery of sensitizing agents for photodynamic therapy.展开更多
In photodynamic therapy(PDT),Ru(Ⅱ)polypyridyl complexes(RPCs)featuring the popularπ-expansive benzo[i]dipyrido[3,2-a:2’,3’-c]phenazine(dppn)ligand have attracted much attention,mainly due to the good singlet oxyge...In photodynamic therapy(PDT),Ru(Ⅱ)polypyridyl complexes(RPCs)featuring the popularπ-expansive benzo[i]dipyrido[3,2-a:2’,3’-c]phenazine(dppn)ligand have attracted much attention,mainly due to the good singlet oxygen sensitizing properties imparted by this peculiar ligand.However,notwithstanding the intriguing perspectives,much remains to be explored about the use of RPC-based photosensitizing agents(PSs)with more than a dppn ligand in their scaffolds.展开更多
文摘Herein,we report on the successful encapsulation into human H-ferritin of two highly charged Ru(Ⅱ)polypyridyl complexes,[Ru(phen)2L’]^(2+)(Ru1,with L’=4,4’-(2,5,8,11,14-pentaaza[15])-2,2’-bipyridilophane)and[Ru(phen)2L’’]^(2+)(Ru2,with L’’=4,4’-bis-[methylen-(1,4,7,10-tetraazacyclododecane)]-2,2’-bipyridine).The resulting Ru(Ⅱ)-ferritin nanocomposites are highly luminescent,display great stability in physiological conditions and preserve the native shell–core structure of the protein.Moreover,the singlet oxygen sensitizing properties of metal complexes,established by independent spectrophotometric and spectrofluorimetric measurements,are largely maintained also in their encapsulated form.Ru(Ⅱ)-ferritin nanocomposites are exclusively internalized by cancer cells expressing the transferrin receptor 1(TfR1)(i.e.HeLa and A2780 with respect to non-cancerous C2C12 myoblasts).Immunofluorescence analysis also reveals the co-localization of Ru1 and Ru2 with the TfR1 in the internal cellular compartments of HeLa and A2780 cells,highlighting the crucial role played by the receptor-mediated endocytosis of H-type ferritins exerted by TfR1.Finally,an MTT assay probed that light-activation effectively leads to a marked dose-dependent cytotoxic effect uniquely against cancer cells.This study underlines the potential of human H-ferritin as a valuable tool for the tumor-targeted delivery of sensitizing agents for photodynamic therapy.
基金Department of Chemistry Ugo Schiff of the University of Florence for the Cryo-TEM measurements.UniCA-Progetti biennali di Ateno Finanziati dalla Fondazione di Sardegna 2018(CUP F741I19000950007)is gratefully acknowledged for(partial)financial support.
文摘In photodynamic therapy(PDT),Ru(Ⅱ)polypyridyl complexes(RPCs)featuring the popularπ-expansive benzo[i]dipyrido[3,2-a:2’,3’-c]phenazine(dppn)ligand have attracted much attention,mainly due to the good singlet oxygen sensitizing properties imparted by this peculiar ligand.However,notwithstanding the intriguing perspectives,much remains to be explored about the use of RPC-based photosensitizing agents(PSs)with more than a dppn ligand in their scaffolds.
