As a“cold tumor”,triple-negative breast cancer(TNBC)exhibits limited responsiveness to current immunotherapy.How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a form...As a“cold tumor”,triple-negative breast cancer(TNBC)exhibits limited responsiveness to current immunotherapy.How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a formidable challenge.Herein,an“in situ nanovaccine”Au/CuNDs-R848 was designed for imagingguided photothermal therapy(PTT)/chemodynamic therapy(CDT)synergistic therapy to trigger dual immunoregulatory effects on TNBC.On the one hand,Au/CuNDs-R848 served as a promising photothermal agent and nanozyme,achieving PTT and photothermal-enhanced CDT against the primary tumor of TNBC.Meanwhile,the released antigens and damage-associated molecular patterns(DAMPs)promoted the maturation of dendritic cells(DCs)and facilitated the infiltration of T lymphocytes.Thus,Au/CuNDs-R848 played a role as an“in situ nanovaccine”to enhance the immunogenicity of TNBC by inducing immunogenic cell death(ICD).On the other hand,the nanovaccine suppressed the myeloid-derived suppressor cells(MDSCs),thereby reversing the immunosuppressive microenvironment.Through the dual immunoregulation,“cold tumor”was transformed into a“hot tumor”,not only implementing a“turning foes to friends”therapeutic strategy but also enhancing immunotherapy against metastatic TNBC.Furthermore,Au/CuNDs-R848 acted as an excellent nanoprobe,enabling high-resolution near-infrared fluorescence and computed tomography imaging for precise visualization of TNBC.This feature offers potential applications in clinical cancer detection and surgical guidance.Collectively,this work provides an effective strategy for enhancing immune response and offers novel insights into the potential clinical applications for tumor immunotherapy.展开更多
基金supported by the National Key Research and Development Program of China(2022YFC2504200)the National Natural Science Foundation of China(Nos.82270959 and 81970903)+5 种基金the Natural Science Foundation of Jilin Province(No.SKL202302002)the Key Research and Development Project of Jilin Provincial Science and Technology Department(Nos.20210204142YY)the Jilin University Norman Bethune Program(No.2023B28)the Fundamental Research Funds for the Central Universities,the Natural Science Foundation of Liaoning Province(No.2022-BS-123)the Science and Technology Project of Shenyang(No.21-173-9-34)“Medical+X”Interdisciplinary Innovation Team“Announcement and Leadership”Construction Project(2022JBGS08).
文摘As a“cold tumor”,triple-negative breast cancer(TNBC)exhibits limited responsiveness to current immunotherapy.How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a formidable challenge.Herein,an“in situ nanovaccine”Au/CuNDs-R848 was designed for imagingguided photothermal therapy(PTT)/chemodynamic therapy(CDT)synergistic therapy to trigger dual immunoregulatory effects on TNBC.On the one hand,Au/CuNDs-R848 served as a promising photothermal agent and nanozyme,achieving PTT and photothermal-enhanced CDT against the primary tumor of TNBC.Meanwhile,the released antigens and damage-associated molecular patterns(DAMPs)promoted the maturation of dendritic cells(DCs)and facilitated the infiltration of T lymphocytes.Thus,Au/CuNDs-R848 played a role as an“in situ nanovaccine”to enhance the immunogenicity of TNBC by inducing immunogenic cell death(ICD).On the other hand,the nanovaccine suppressed the myeloid-derived suppressor cells(MDSCs),thereby reversing the immunosuppressive microenvironment.Through the dual immunoregulation,“cold tumor”was transformed into a“hot tumor”,not only implementing a“turning foes to friends”therapeutic strategy but also enhancing immunotherapy against metastatic TNBC.Furthermore,Au/CuNDs-R848 acted as an excellent nanoprobe,enabling high-resolution near-infrared fluorescence and computed tomography imaging for precise visualization of TNBC.This feature offers potential applications in clinical cancer detection and surgical guidance.Collectively,this work provides an effective strategy for enhancing immune response and offers novel insights into the potential clinical applications for tumor immunotherapy.
