Immune microenvironment-reshaping Au@Bi2Te3 nanoparticles for spectral computed tomography/photoacoustic imaging-guided synergetic photo/radio/immunotherapy

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@Bi2Te3-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@Bi2Te3-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 CD4+ and CD8+ T cells 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@Bi2Te3-PEG NPs could serve as effective theranostic nanoregulators with remarkable synergistic mild-photothermal/RT/immunotherapy effects that helped reshape the immune microenvironment and had remarkable molecular imaging properties.