Active targeting of orthotopic glioma using biomimetic liposomes co-loaded elemene and cabazitaxel modified by transferritin

J Nanobiotechnology. 2021 Sep 26;19(1):289. doi: 10.1186/s12951-021-01048-3.

Abstract

Background: Effective treatment of glioma requires a nanocarrier that can cross the blood-brain barrier (BBB) to target the tumor lesion. In the current study, elemene (ELE) and cabazitaxel (CTX) liposomes were prepared by conjugating liposomes with transferrin (Tf) and embedding the cell membrane proteins of RG2 glioma cells into liposomes (active-targeting biomimetic liposomes, Tf-ELE/CTX@BLIP), which exhibited effective BBB infiltration to target glioma.

Results: The findings showed that Tf-ELE/CTX@BLIP was highly stable. The liposomes exhibited highly significant homologous targeting and immune evasion in vitro and a 5.83-fold intake rate compared with classical liposome (ELE/CTX@LIP). Bioluminescence imaging showed increased drug accumulation in the brain and increased tumor penetration of Tf-ELE/CTX@BLIP in orthotopic glioma model nude mice. Findings from in vivo studies indicated that the antitumor effect of the Tf-ELE/CTX@BLIP led to increased survival time and decreased tumor volume in mice. The average tumor fluorescence intensity after intravenous administration of Tf-ELE/CTX@BLIP was 65.2, 12.5, 22.1, 6.6, 2.6, 1.5 times less compared with that of the control, CTX solution, ELE solution, ELE/CTX@LIP, ELE/CTX@BLIP, Tf-ELE/CTX@LIP groups, respectively. Histopathological analysis showed that Tf-ELE/CTX@BLIP were less toxic compared with administration of the CTX solution.

Conclusion: These findings indicate that the active-targeting biomimetic liposome, Tf-ELE/CTX@BLIP, is a promising nanoplatform for delivery of drugs to gliomas.

Keywords: Biomimetic liposomes; Blood–brain barrier; Glioma; Homologous-targeting; Immune escaping; Transferrin.

MeSH terms

  • Animals
  • Biological Transport
  • Biomimetics / methods*
  • Blood-Brain Barrier / metabolism
  • Brain
  • Cell Line, Tumor
  • Drug Delivery Systems / methods
  • Glioma / pathology
  • Glioma / therapy*
  • Liposomes / administration & dosage*
  • Mice
  • Mice, Nude
  • Sesquiterpenes / metabolism
  • Sesquiterpenes / pharmacology*
  • Sesquiterpenes / therapeutic use
  • Taxoids / metabolism
  • Taxoids / pharmacokinetics*
  • Taxoids / therapeutic use
  • Transferrin / metabolism*
  • Transferrin / pharmacology
  • Transferrin / therapeutic use

Substances

  • Liposomes
  • Sesquiterpenes
  • Taxoids
  • Transferrin
  • elemene
  • cabazitaxel