Although immunogenic cell death(ICD)has garnered significant attention in the realm of“cold”tumor therapies,effectively stimulating strong immune responses with minimal side effects,their real-time monitoring in dee...Although immunogenic cell death(ICD)has garnered significant attention in the realm of“cold”tumor therapies,effectively stimulating strong immune responses with minimal side effects,their real-time monitoring in deep-seated tumors remains challenging.There is no available drug that covers these two bases with one swing.Herein,we report a proof-of-concept for the rational design and synthesis of a novel class of five redox-active iron(III)complexes,([Fe^(III)(L1-L5)_(2)]),based on sirtinol analogs bearing adamantane moieties.These complexes show potential as modest stimulators of ICD,as indicated by the expression of key ICD markers.The lead compound,Fe(L1)_(2),exhibits promiscuous nanoscale aggregation in RPMI-1640 cell culture media,characterized by a stable hydrodynamic effective diameter ranging from 50 nm to 70 nm over 48 hours.Fe(L1)_(2) nanoaggregates with enhanced efficacy against MCF-7 cells undergo an energy-dependent endocytic cellular-uptake pathway.In our proposed two-for-one approach,the DAMP marker indicates that our Fe(L1)_(2) nanoaggregates are iron-based complexes that warm up the tumor environment by maximizing the antitumor immune response,and Fe(L1-L3)_(2) display well-defined photoacoustic NIR-II spectra that underscore their suitability in future for high-resolution imaging applications.展开更多
基金supported by the The Indian Council of Medical Research(ICMR),Anusandhan National Research Foundation(ANRF),DST SERB Start-up Research Grant(Grant 2021435)INSPIRE Faculty Research Grant(Grant 2019295)Prime Minister Research Grant(PMRF-ID:2300572).
文摘Although immunogenic cell death(ICD)has garnered significant attention in the realm of“cold”tumor therapies,effectively stimulating strong immune responses with minimal side effects,their real-time monitoring in deep-seated tumors remains challenging.There is no available drug that covers these two bases with one swing.Herein,we report a proof-of-concept for the rational design and synthesis of a novel class of five redox-active iron(III)complexes,([Fe^(III)(L1-L5)_(2)]),based on sirtinol analogs bearing adamantane moieties.These complexes show potential as modest stimulators of ICD,as indicated by the expression of key ICD markers.The lead compound,Fe(L1)_(2),exhibits promiscuous nanoscale aggregation in RPMI-1640 cell culture media,characterized by a stable hydrodynamic effective diameter ranging from 50 nm to 70 nm over 48 hours.Fe(L1)_(2) nanoaggregates with enhanced efficacy against MCF-7 cells undergo an energy-dependent endocytic cellular-uptake pathway.In our proposed two-for-one approach,the DAMP marker indicates that our Fe(L1)_(2) nanoaggregates are iron-based complexes that warm up the tumor environment by maximizing the antitumor immune response,and Fe(L1-L3)_(2) display well-defined photoacoustic NIR-II spectra that underscore their suitability in future for high-resolution imaging applications.
