Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence

Abstract

Cell-mediated drug-delivery systems have received considerable attention for their enhanced therapeutic specificity and efficacy in cancer treatment. Neutrophils (NEs), the most abundant type of immune cells, are known to penetrate inflamed brain tumours. Here we show that NEs carrying liposomes that contain paclitaxel (PTX) can penetrate the brain and suppress the recurrence of glioma in mice whose tumour has been resected surgically. Inflammatory factors released after tumour resection guide the movement of the NEs into the inflamed brain. The highly concentrated inflammatory signals in the brain trigger the release of liposomal PTX from the NEs, which allows delivery of PTX into the remaining invading tumour cells. We show that this NE-mediated delivery of drugs efficiently slows the recurrent growth of tumours, with significantly improved survival rates, but does not completely inhibit the regrowth of tumours.

Cxcr1 mediates recruitment of neutrophils and supports proliferation of tumor-initiating astrocytes in vivo

“…Our data suggest that targeting neutrophil chemotaxis and tumor infiltration could provide a useful avenue for developing future clinical targets. One exciting new approach is exploiting neutrophils’ highly migratory and tumor-infiltrative capabilities to target drugs to the TME 59 . In a recent study by Xue et al ., primary mouse neutrophils loaded with liposomes containing paclitaxel were injected into the blood stream of a glioma mouse model post-tumor resection, resulting in neutrophil homing to the brain, release of the drug, and ultimately increased survival in treated mice.…”

Photosensitizer Micelles Together with IDO Inhibitor Enhance Cancer Photothermal Therapy and Immunotherapy

“…The ongoing development of nanoparticles not only improves the targeting and bioavailability of drugs and develops new therapeutic methods, such as photothermal therapy and nanovaccines, but also provides a suitable carrier for the realization of combination therapy 2, 3, 4, 5, 6, 7. Moreover, some nanoparticle‐based systems can strengthen the immune response in tumor immunotherapy, which has attracted much attention 8, 9, 10, 11…”

Immunomodulating Nanomedicine for Cancer Therapy

“…Nanoparticles loaded with chemotherapeutic agents were delivered into neutrophils, which are then recruited to resection bed of brain tumors by postsurgical inflammatory cytokines to release the drugs that reduce local recurrences. 18 This immune-cell-based tumor targeting strategy also applies to other innate immune cell subtypes. For example, directly conjugating anti-PD-L1 antibodies onto the plasma membrane of platelets, which accumulate in the resection cavity after tumor surgery, can significantly facilitate the delivery of the antibody to the surgical bed, leading to reduced local and distant recurrence risks and prolonged survival in tumor-bearing mice.…”