Real time in vivo efficacy monitoring of desialylation and perforation enhanced immunotherapy of cancer

Abstract Efficient enhanced NK cell therapy is of critical importance in the immune treatment of cancer. Real time monitoring provides the necessary means for precise treatment and improving its efficacy. This work designed a powerful nanomedicine (MFMAF‐7) to engineer NK cells for perforation and desialylation by encapsulating streptolysin O conjugated neuraminidase, adenosinetriphosphate (ATP)‐responsive DNA and granzyme B (GrB)‐responsive peptide (SLO‐NEU, SLO‐AD, SLO‐GP) in cholesterol and aptamer‐modified zeolitic metal azolate framework‐7. After targeted delivery of the engineered NK cells to tumor region, the nanomedicine is degraded to release SLO‐NEU, SLO‐AD and SLO‐GP, which then perforate tumor cells to promote the delivery of cytokines. The anchored SLO‐NEU can cleave sialic acids for inhibiting the immune evasion of tumor cells and activating the NK cells to release cytokines, while the SLO‐AD and SLO‐GP can in situ visualize the levels of both ATP and GrB for assessing the efficacy in real time. The in vivo experiments with tumor‐bearing mice demonstrate the enhanced efficacy of immunotherapy and the feasibility of real time monitoring with the proposed nanomedicine.