Programmable Chemotherapy and Immunotherapy against Breast Cancer Guided by Multiplexed Fluorescence Imaging in the Second Near-Infrared Window

摘要

Combined chemotherapy and immunotherapy have demonstrated great potential in cancer treatment. However, it is difficult to provide clear information of the pharmacokinetics and pharmacodynamics of chemodrugs and transplanted immune cells in vivo by traditional approaches, resulting in inadequate therapy. Here, a multiplexed intravital imaging strategy by using fluorescence in the second near-infrared window (NIR-II) is first developed to visualize the two events of chemotherapy and immunotherapy in vivo, so that a combinational administration is programed to improve the therapeutical effects against a mouse model of human breast cancer. In detail, Ag2Se quantum dots (QDs) (lambda(Em) = 1350 nm) loaded with stromal-cell-derived factor-1 alpha (SDF-1 alpha) and chemodrug doxorubicin (DOX) are first administrated to deliver the SDF-1 alpha and DOX to the tumor site. After their arrival, monitored by Ag2Se QD fluorescence, natural killer (NK)-92 cells labeled with Ag2S QDs (lambda(Em) = 1050 nm) are intravenously injected so that the cells are recruited to the tumor by the chemotaxis of SDF-1 alpha, which is visualized by Ag2S QD fluorescence. Such an imaging approach allows simultaneous evaluation of the behaviors of individual injections in vivo, and facilitates optimized administration regimens, resulting in enhanced tumor inhibition.