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Research Activity

Research conducted in lab

SapC-DOPS as a nanodrug for treatment of cancer

The Theragnostic Drug and Biomarker Discovery laboratory conducts translational cancer research aimed at developing diagnostic and therapeutic agents for solid tumors. Work in the lab has led to the development of nanovesicles composed of the naturally-occurring protein saposin C and the phospholipid dioleoylphosphatidylserine (DOPS), termed SapC-DOPS, which selectively target and kill cancer cells. The basis for this selectivity is the abundant expression of phosphatidylserine in the outer membrane of diverse tumor cells and their associated vasculature, to which SapC-DOPS bind. In healthy cells, in contrast, phosphatidylserine is distributed asymmetrically, with greater abundance on the inside layer of the plasma membrane. When coupled to fluorescent or paramagnetic compounds, SapC-DOPS have been successfully used for tumor imaging in animal models. Effective targeting and killing of tumor cells has been shown in mouse models of primary (glioblastoma) and metastatic brain cancer, pancreatic cancer, lung tumor, breast tumor, melanoma, neuroblastoma and malignant peripheral nerve sheath tumor. SapC-DOPS induces apoptotic and/or lysosomal cancer cell death.

SapC-DOPS as a brain-targeted drug delivery nanosystem for the treatment of Gaucher disease

Gaucher disease is a rare genetic disease caused by the mutations of GBA1 gene encoding lysosomal enzyme, acid -glucosidase (GCase). A major limitation of FDA approved enzyme replacement therapy is failure to cross the blood-brain barrier (BBB). Therefore, the currently available treatments are only effective on the visceral manifestations of Gaucher disease and are completely ineffective for Types 2 and 3 neuronopathic central nervous system (CNS) variants that present often early in life with high mortality. Lab with collaboration with Dr. Ying Sun at Cincinnati Children’s Hospital showed that SapC-DOPS-GCase nanocomplex successfully cross the BBB and selectively target the neural tissue, providing a biological SapC-based lipid nanocarrier for delivering GCase into the CNS.

Immunotherapeutic approach to combat cancer

A hallmark feature of malignant cell growth is the presence of an immunosuppressive tumor microenvironment (TME). Immunosuppressive M2 macrophages (MØs) in the TME facilitate tumor escape from immune surveillance and sustain tumor growth. Lab have discovered a cancer-secreted protein that promotes immunosuppressive MØ M2 polarization. Of potential therapeutic importance, lab discovered that a lipid-based nanodrug inhibits intra-tumor M2 MØ polarization and tumor growth by sequestering the cancer-released protein.

Modulation of surface biomarker of cancer to sensitize them against current available treatments

The use of electric field is gaining attention in the fight against cancer, yet current available modalities are limited to electroporation and tumor treating electric field. Although biomarker-driven cancer therapy has seen a growing interest in cancer treatment, there is a critical gap between targeting cancer related biomarkers and enhancing biomarker matched targeting therapies, by using electric field. Importantly, it has been shown in multiple studies that increasing cancer biomarker, cell surface phosphatidylserine (PS) exposure using chemo- or radiation-therapy is a logical approach to sensitize the cancer cells to PS-targeting drugs. However, these combinations have the drawback of potentially harming healthy cells. Lab has developed a method for altering the surface PS levels in cancer cells using electric field without killing the cells. This project aims to sensitize the cancer cells to current available treatment modalities such as chemotherapy/radiotherapy and PS-targeting treatments such as SapC-DOPS nanodrugs.

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University of Cincinnati
Department of Internal Medicine

Division of Hematology & Oncology
231 Albert Sabin Way, ML 0562
Cincinnati, OH 45267-0562

Phone: 513-558-2115
Fax: 513-558-2125