The intense metabolism of cancer cells leads to hypoxia and lack of crucial nutrients in the tumor microenvironment, which hinders the function of immune cells. We designed a biomimetic immune metabolic nanoplatform, in which a type I aggregation-induced emission photosensitizer and a glutamine antagonist are encapsulated into a cancer cell membrane for achieving specific delivery in vivo. This approach greatly satisfies the glucose and glutamine required by T cells, significantly improves the tumor hypoxic environment, enables the reprogramming of tumor and immune cell metabolism, induces immunogenic cell death, promotes dendritic cell maturation, and effectively inhibits tumor proliferation. Strong tumor-specific immune responses are further triggered, and the tumor immune-suppressing microenvironment is modulated, by decreasing the number of immunosuppressive cells. Moreover, subsequent combination with anti-PD-1 is able to generate strong abscopal effects to prevent tumor distant metastasis and provide long-term immune memory against tumor recurrence.
Copper ions (Cu2+) and l-cysteine (l-Cys) in the human body always play critical roles in various physiological processes, while abnormal Cu2+ and l-Cys concentrations in the biological system lead to many diseases.
Circulating tumor cells (CTCs) are rare, meaning that current isolation strategies can hardly satisfy efficiency and cell biocompatibility requirements, which hinders clinical applications. In addition, the selected cells require immunofluorescence identification, which is a time-consuming and expensive process. Here, we developed a method to simultaneously separate and identify CTCs by the integration of optical force and fluorescent microspheres. Our method achieved high-purity separation of CTCs without damage through light manipulation and avoided additional immunofluorescence staining procedures, thus achieving rapid identification of sorted cells. White blood cells (WBCs) and CTCs are similar in size and density, which creates difficulties in distinguishing them optically. Therefore, fluorescent PS microspheres with high refractive index (RI) are designed here to capture the CTCs (PS-CTCs) and increase the average index of refraction of PS-CTCs. In optofluidic chips, PS-CTCs were propelled to the collection channel from the sample mixture, under the radiation of light force. Cells from the collection outlet were easily identified under a fluorescence microscope due to the fluorescence signals of PS microspheres. This method provides an approach for the sorting and identification of CTCs, which holds great potential for clinical applications in early diagnosis of disease.
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