Targeting neutrophils potentiates hitchhiking delivery of drugs and agonists for postsurgical chemo-immunotherapy

Abstract

Tumor resection is usually associated with tumor recurrence due to the residual tumor cells. Improving the localized accumulation of therapeutics at the surgical sites is a promising approach for the inhibition of tumor recurrence and metastasis. Herein, we report an in situ hitchhiking strategy for postsurgical tumor therapy via targeting of therapeutics-loaded liposomes to neutrophils (NEs). Anticancer drug doxorubicin (DOX) and non-nucleotide stimulator of interferon genes (STING) agonist SR-717 are encapsulated into liposomes followed by surface modification with anti-Ly6G antibodies, which can target NEs in situ in blood stream for hitchhiking delivery to the postsurgical inflamed tumor sites. The delivered DOX can inhibit the growth of residual tumor cells and trigger the tumor immunogenic cell death (ICD) for tumor-specific immunity, while SR-717 can facilitate dendritic cell maturation and enhance antitumor immunity. Consequently, the in situ NE-hitchhiking delivery of therapeutics can efficiently suppress tumor recurrence and metastatic melanoma growth after tumor resection, which circumvents the complex ex vivo processes of separation, engineering, and refusion of leukocytes and represents a targeted delivery strategy for postsurgical cancer chemo-immunotherapy.