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All-stage targeted therapy for glioblastoma based on lipid membrane coated cabazitaxel nanocrystals

Sunyi Wu1, Linwei Lu2, Jianfen Zhou1

  • 1Department of Pharmaceutics, School of Pharmacy, & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education and PLA, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|March 29, 2022
PubMed

Insights

This study introduces a novel liposome nanoparticle delivering cabazitaxel (CBZ) that effectively targets glioblastoma (GBM) by crossing the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). The targeted therapy significantly improved survival in a preclinical GBM model.

Area of Science:

  • Nanomedicine
  • Oncology
  • Neuroscience

Background:

  • Glioblastoma (GBM) is an aggressive brain tumor with high recurrence rates.
  • The blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) impede drug delivery to gliomas.
  • Vasculogenic mimicry (VM) in GBM contributes to tumor recurrence.

Purpose of the Study:

  • To develop an all-stage glioma-targeted cabazitaxel (CBZ) nanocrystal loaded liposome (pV-Lip/cNC).
  • To overcome the BBB, BBTB, and VM challenges for enhanced GBM therapy.
  • To evaluate the efficacy of pV-Lip/cNC in a murine orthotopic GBM model.

Main Methods:

  • Development of a "Y" shaped targeting ligand using p-hydroxybenzoic acid (pHA) and VAP peptide.
  • Formulation of CBZ nanocrystals within a liposome structure.
  • In vitro assessment of glioma homing, barrier crossing, and spheroid penetration.
  • In vivo evaluation of therapeutic efficacy and survival in a murine GBM model.

Main Results:

  • pV-Lip/cNC demonstrated excellent in vitro glioma targeting and penetration capabilities.
  • The formulation successfully traversed the BBB and BBTB in vivo.
  • Treatment with pV-Lip/cNC significantly increased median survival time (53 days) compared to controls.
  • Enhanced CBZ accumulation in the glioma region was observed.

Conclusions:

  • The developed pV-Lip/cNC is a promising nanomedicine for overcoming GBM therapeutic barriers.
  • This targeted liposomal delivery system effectively targets and treats glioblastoma.
  • pV-Lip/cNC holds potential for improving outcomes in all stages of glioma therapy.
Keywords:
All-stage targeted deliveryCabazitaxelGliomaLiposomeNanocrystal

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