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In Vivo Optical Imaging of Brain Tumors and Arthritis Using Fluorescent SapC-DOPS Nanovesicles
Published on: May 2, 2014
Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS nanovesicles on brain tumors
Víctor M Blanco1, Zhengtao Chu2, Subrahmanya D Vallabhapurapu1
1Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Abstract:
Brain tumors, either primary (e.g., glioblastoma multiforme) or secondary (metastatic), remain among the most intractable and fatal of all cancers. We have shown that nanovesicles consisting of Saposin C (SapC) and dioleylphosphatidylserine (DOPS) are able to effectively target and kill cancer cells both in vitro and in vivo. These actions are a consequence of the affinity of SapC-DOPS for phosphatidylserine, an acidic phospholipid abundantly present in the outer membrane of a variety of tumor cells and tumor-associated vasculature. In this study, we first characterize SapC-DOPS bioavailability and antitumor effects on human glioblastoma xenografts, and confirm SapC-DOPS specificity towards phosphatidylserine by showing that glioblastoma targeting is abrogated after in vivo exposure to lactadherin, which binds phosphatidylserine with high affinity. Second, we demonstrate that SapC-DOPS selectively targets brain metastases-forming cancer cells both in vitro, in co-cultures with human astrocytes, and in vivo, in mouse models of brain metastases derived from human breast or lung cancer cells. Third, we demonstrate that SapC-DOPS have cytotoxic activity against metastatic breast cancer cells in vitro, and prolong the survival of mice harboring brain metastases. Taken together, these results support the potential of SapC-DOPS for the diagnosis and therapy of primary and metastatic brain tumors.
Insights
Saposin C (SapC) and dioleylphosphatidylserine (DOPS) nanovesicles effectively target and kill primary and metastatic brain tumors. These novel nanovesicles show promise for brain tumor diagnosis and therapy.
Area of Science:
- Oncology
- Nanomedicine
- Biochemistry
Background:
- Primary and secondary brain tumors are highly fatal and difficult to treat.
- Nanovesicles composed of Saposin C (SapC) and dioleylphosphatidylserine (DOPS) demonstrate potential for cancer cell targeting.
- SapC-DOPS affinity for phosphatidylserine (PS) enables tumor cell and vasculature recognition.
Purpose of the Study:
- To characterize SapC-DOPS bioavailability and efficacy against glioblastoma.
- To evaluate SapC-DOPS targeting specificity for phosphatidylserine.
- To assess SapC-DOPS activity against brain metastases from breast and lung cancers.
Main Methods:
- In vivo studies using human glioblastoma xenografts and mouse models of brain metastases.
- In vitro co-culture experiments with human astrocytes and cancer cells.
- Assessment of SapC-DOPS targeting by lactadherin competition assays.
Main Results:
- SapC-DOPS showed bioavailability and antitumor effects on glioblastoma xenografts.
- Targeting specificity was confirmed by abrogated glioblastoma targeting after lactadherin exposure.
- SapC-DOPS selectively targeted and exhibited cytotoxic activity against brain metastatic cells, prolonging survival in mice.
Conclusions:
- SapC-DOPS nanovesicles demonstrate significant potential for treating primary and metastatic brain tumors.
- The study supports the use of SapC-DOPS for both diagnostic and therapeutic applications in brain oncology.
- Further research into SapC-DOPS is warranted for clinical translation in neuro-oncology.

