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In Vivo Optical Imaging of Brain Tumors and Arthritis Using Fluorescent SapC-DOPS Nanovesicles
Published on: May 2, 2014
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.
Abstract:
Saposin C-dioleoylphosphatidylserine (SapC-DOPS) nanovesicles are a nanotherapeutic which effectively target and destroy cancer cells. Here, we explore the systemic use of SapC-DOPS in several models of brain cancer, including glioblastoma multiforme (GBM), and the molecular mechanism behind its tumor-selective targeting specificity. Using two validated spontaneous brain tumor models, we demonstrate the ability of SapC-DOPS to selectively and effectively cross the blood-brain tumor barrier (BBTB) to target brain tumors in vivo and reveal the targeting to be contingent on the exposure of the anionic phospholipid phosphatidylserine (PtdSer). Increased cell surface expression of PtdSer levels was found to correlate with SapC-DOPS-induced killing efficacy, and tumor targeting in vivo was inhibited by blocking PtdSer exposed on cells. Apart from cancer cell killing, SapC-DOPS also exerted a strong antiangiogenic activity in vitro and in vivo. Interestingly, unlike traditional chemotherapy, hypoxic cells were sensitized to SapC-DOPS-mediated killing. This study emphasizes the importance of PtdSer exposure for SapC-DOPS targeting and supports the further development of SapC-DOPS as a novel antitumor and antiangiogenic agent for brain tumors.
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.
