Tumor Microenvironment Activated Photoacoustic-Fluorescence Bimodal Nanoprobe for Precise Chemo-immunotherapy and Immune Response Tracing of Glioblastoma.

Synergistic therapy strategy and prognostic monitoring of glioblastoma's immune response to treatment are crucial to optimize patient care and advance clinical outcomes. However, current systemic temozolomide (TMZ) chemotherapy and imaging methods for in vivo tracing of immune responses are inadequate. Herein, we report an all-in-one theranostic nanoprobe (PEG/αCD25-Cy7/TMZ) for precise chemotherapy and real-time immune response tracing of glioblastoma by photoacoustic-fluorescence imaging. The nanoprobe was loaded with TMZ and targeted regulatory T lymphocyte optical dye αCD25-Cy7 encapsulated by glutathione-responsive DSPE-SS-PEG2000. The results showed that the targeted efficiency of the nanoprobe to regulatory T lymphocytes is up to 92.3%. The activation of PEG/αCD25-Cy7/TMZ by glutathione enhanced the precise delivery of TMZ to the tumor microenvironment for local chemotherapy and monitored glioblastoma's boundary by photoacoustic-fluorescence imaging. Immunotherapy with indoleamine 2,3-dioxygenase inhibitors after chemotherapy could promote immunological responses and reduce regulatory T lymphocyte infiltration, which could improve the survival rate. Photoacoustic imaging has in real-time and noninvasively depicted the dynamic process of immune response on a micrometer scale, showing that the infiltration of regulatory T lymphocytes after chemotherapy was up-regulated and would down-regulate after IDO inhibitor treatment. This all-in-one theranostic strategy is a promising method for precisely delivering TMZ and long-term dynamically tracing regulatory T lymphocytes to evaluate the immune response in situ for accurate tumor chemo-immunotherapy.