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

Nat Nanotechnol. 2017 Jul;12(7):692-700. doi: 10.1038/nnano.2017.54. Epub 2017 Jun 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacokinetics
  • Antineoplastic Agents* / pharmacology
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Brain Neoplasms / prevention & control*
  • Cell Line, Tumor
  • Drug Delivery Systems / methods*
  • Glioma / metabolism
  • Glioma / pathology
  • Glioma / prevention & control*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / prevention & control*
  • Neutrophils*
  • Paclitaxel* / chemistry
  • Paclitaxel* / pharmacokinetics
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Paclitaxel