Tumor targeted combination therapy mediated by functional macrophages under fluorescence imaging guidance

Abstract

Imaging-guiding and targeted drug delivery to tumors are essential for precision cancer therapy, which is a challenging goal to achieve extraordinary therapeutic efficacy. Functional live cells-based delivery systems are expected to play an important role in imaging-guiding and targeted drug delivery. Herein, we fabricated a delivery system mediated by IR-820 conjugated macrophages for tumor targeted combination therapy under fluorescence imaging guidance. The functional macrophages by nature could cross the barriers and recruit into tumors, and serve as host cells to targeted deliver drugs to tumors. The pH-sensitive doxorubicin nanoparticles were engulfed by the macrophages to enhance the drug loading and decrease the damage on host cells. IR-820 was anchored into macrophages cytoplasm to achieve the dual function of photothermal therapy and fluorescence imaging guidance. With Balb/C mice bearing murine breast tumor (4 T1) as models, the functional macrophages for their innate tumor tropism could targeted transport these therapeutic drugs into tumor site to exert efficient chemo-photothermal combination therapy. Moreover, fluorescence imaging-guided drug delivery was employed as the visible strategy to provide the optimized therapeutic window based on the fluorescence of IR-820. The multi-functional macrophages-mediated delivery system would provide a potential for precise and targeted delivery of combination therapy.

Keywords: Chemo-photothermal combination therapy; IR-820; Imaging guidance; Macrophages; Tumor targeted delivery.