Transferrin Receptor-Targeted PEG-PLA Polymeric Micelles for Chemotherapy Against Glioblastoma Multiforme

Int J Nanomedicine. 2020 Sep 11:15:6673-6688. doi: 10.2147/IJN.S257459. eCollection 2020.

Abstract

Background: The safe and efficient delivery of chemotherapeutic agents is critical to glioma therapy. However, chemotherapy for glioma is extremely challenging because the blood-brain barrier (BBB) rigorously prevents drugs from reaching the tumor region.

Materials and methods: TfR-T12 peptide-modified PEG-PLA polymer was synthesized to deliver paclitaxel (PTX) for glioma therapy. TfR was significantly expressed on brain capillary endothelial cells and glioma cells; therefore, TfR-T12 peptide-modified micelles can cross the BBB system and target glioma cells.

Results: TfR-T12-PEG-PLA/PTX polymeric micelles (TfR-T12-PMs) could be absorbed rapidly by tumor cells, and traversed effectively the BBB monolayers. TfR-T12-PMs can effectively inhibit the proliferation of U87MG cells in vitro, and TfR-T12-PMs loaded with paclitaxel presented better antiglioma effect with prolonged median survival of nude mice-bearing glioma than the unmodified PMs.

Conclusion: The TfR-T12-PMs could effectively overcome the BBB barrier and accomplish glioma-targeted drug delivery, thus validating its potential in improving the therapeutic outcome in multiforme.

Keywords: BBB transcytosis effect; glioblastoma multiforme; polymeric micelles; targeted delivery; transferrin receptor.

MeSH terms

  • Animals
  • Antigens, CD
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Blood-Brain Barrier / drug effects
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Delivery Systems / methods*
  • Endothelial Cells / metabolism
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Micelles*
  • Paclitaxel / administration & dosage
  • Paclitaxel / pharmacology
  • Peptides / chemistry
  • Polyethylene Glycols / chemistry
  • Receptors, Transferrin / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, CD
  • Antineoplastic Agents, Phytogenic
  • CD71 antigen
  • Micelles
  • Peptides
  • Receptors, Transferrin
  • monomethoxypolyethyleneglycol-polylactide block copolymer
  • Polyethylene Glycols
  • Paclitaxel