Systemic delivery of SapC-DOPS has antiangiogenic and antitumor effects against glioblastoma

Jeffrey Wojton1, Zhengtao Chu, Haritha Mathsyaraja

  • 1Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurological Surgery, The Ohio State University Medical Center, Columbus, Ohio 43210, USA.

Insights

Saposin C-dioleoylphosphatidylserine (SapC-DOPS) nanovesicles target brain tumors by recognizing exposed phosphatidylserine (PtdSer). This nanotherapeutic shows anti-tumor and anti-angiogenic effects, even in hypoxic cancer cells.

Area of Science:

  • Nanomedicine
  • Oncology
  • Molecular Biology

Background:

  • Saposin C-dioleoylphosphatidylserine (SapC-DOPS) nanovesicles are a promising nanotherapeutic for cancer treatment.
  • Glioblastoma multiforme (GBM) presents significant challenges due to the blood-brain tumor barrier (BBTB).

Purpose of the Study:

  • To investigate the systemic use of SapC-DOPS in brain cancer models.
  • To elucidate the molecular mechanism of SapC-DOPS tumor-selective targeting.
  • To evaluate the anti-tumor and anti-angiogenic activities of SapC-DOPS.

Main Methods:

  • Utilized two validated spontaneous brain tumor models.
  • Assessed SapC-DOPS penetration of the blood-brain tumor barrier (BBTB) in vivo.
  • Quantified cell surface phosphatidylserine (PtdSer) exposure and its correlation with efficacy.
  • Evaluated antiangiogenic activity in vitro and in vivo.
  • Investigated the effect of SapC-DOPS on hypoxic cancer cells.

Main Results:

  • SapC-DOPS effectively crossed the BBTB to target brain tumors.
  • Targeting specificity is contingent on exposed phosphatidylserine (PtdSer) on cancer cells.
  • Increased PtdSer exposure correlated with enhanced SapC-DOPS-induced cancer cell killing.
  • SapC-DOPS demonstrated significant antiangiogenic activity.
  • Hypoxic cancer cells were sensitized to SapC-DOPS treatment.

Conclusions:

  • Phosphatidylserine (PtdSer) exposure is critical for SapC-DOPS targeting in brain tumors.
  • SapC-DOPS exhibits potent anti-tumor and anti-angiogenic properties.
  • Further development of SapC-DOPS as a novel agent for brain tumors is supported.