Radiotherapy(RT)mediated tumor immunogenicity offers an opportunity for simultaneous RT and immunotherapy via immunogenic cell death(ICD),which releases damaged-associated molecular patterns and generates“eat me”sig...Radiotherapy(RT)mediated tumor immunogenicity offers an opportunity for simultaneous RT and immunotherapy via immunogenic cell death(ICD),which releases damaged-associated molecular patterns and generates“eat me”signals for the innate immune system to modulate the immunogenicity.However,tumor hypoxia significantly reduces the therapeutic efficacy of RT and hampers its mediation of ICD induction.Herein,Au@Bi_(2)Te_(3)-polyethylene glycol(PEG)was rationally constructed as theranostic nanozymes for mild photothermal therapy,tumor hypoxia modulation,and RT adjuvant cancer immunotherapy.The tumor-specific production of oxygen could not only augment the effects of RT by enhanced reactive oxygen species(ROS)generation,but also reduce hypoxia-related cytokines and downregulate programmed cell death-ligand 1(PD-L1)to unleash immune-enhancing T cells.Moreover,Au@Bi_(2)Te_(3)-PEG could act as an immune-blocking inhibitor by efficient ICD induction with the combination of mild-photothermal therapy+RT to inhibit the tumor immune escape and improve antitumor immune response.Increased amounts of CD^(4+) and CD^(8+) Tcells and elevated levels of cytokines could be observed that eventually led to effective post-medication inhibition of primary and abscopal tumors.Spectral computed tomography/photoacoustic imaging allowed noninvasive and real-time tracking of nanoparticle(NP)accumulation and oxygenation status at tumor sites.Collectively,Au@Bi_(2)Te_(3)-PEG NPs could serve as effective theranostic nanoregulators with remarkable synergistic mildphotothermal/RT/immunotherapy effects that helped reshape the immune microenvironment and had remarkable molecular imaging properties.展开更多
基金This work was supported by the National Natural Science Foundation of China(Nos.81871334,81801764,82072056,and 51937010)the Guangdong Basic and Applied Basic Research Foundation(Nos.2017A050506011,2018030310343,2020B1515020008,2021A1515012542,and 2021A1515011882)+1 种基金the Medical Scientific Research Foundation of Guangdong Province(No.A2018014)the Pearl River Talented Young Scholar Program(No.2017GC010282).
文摘Radiotherapy(RT)mediated tumor immunogenicity offers an opportunity for simultaneous RT and immunotherapy via immunogenic cell death(ICD),which releases damaged-associated molecular patterns and generates“eat me”signals for the innate immune system to modulate the immunogenicity.However,tumor hypoxia significantly reduces the therapeutic efficacy of RT and hampers its mediation of ICD induction.Herein,Au@Bi_(2)Te_(3)-polyethylene glycol(PEG)was rationally constructed as theranostic nanozymes for mild photothermal therapy,tumor hypoxia modulation,and RT adjuvant cancer immunotherapy.The tumor-specific production of oxygen could not only augment the effects of RT by enhanced reactive oxygen species(ROS)generation,but also reduce hypoxia-related cytokines and downregulate programmed cell death-ligand 1(PD-L1)to unleash immune-enhancing T cells.Moreover,Au@Bi_(2)Te_(3)-PEG could act as an immune-blocking inhibitor by efficient ICD induction with the combination of mild-photothermal therapy+RT to inhibit the tumor immune escape and improve antitumor immune response.Increased amounts of CD^(4+) and CD^(8+) Tcells and elevated levels of cytokines could be observed that eventually led to effective post-medication inhibition of primary and abscopal tumors.Spectral computed tomography/photoacoustic imaging allowed noninvasive and real-time tracking of nanoparticle(NP)accumulation and oxygenation status at tumor sites.Collectively,Au@Bi_(2)Te_(3)-PEG NPs could serve as effective theranostic nanoregulators with remarkable synergistic mildphotothermal/RT/immunotherapy effects that helped reshape the immune microenvironment and had remarkable molecular imaging properties.
