Characterization of rHDL Nanoparticles as a Delivery Vehicle for Glioblastoma Multiforme Chemotherapy

Purpose: Glioblastoma Multiforme (GBM), is a brain tumor that presents with a very poor prognosis; new approaches are needed to improve patient outcomes. Design of an effective therapeutic approach must include a suitable delivery vehicle, which can cross the blood-brain barrier, and can selectively target GBM tumors. Our project uses reconstituted high-density lipoprotein (rHDL) nanoparticles (NPs), which possess the above characteristics, amplifying efficacy of chemotherapy. To target the PI3K/mTOR pathway involved in the pathophysiology of GBM, we chose to encapsulate PI-103 in preliminary studies. Methods: After encapsulation and purification, the drug-containing rHDL NPs will be characterized with regard to their physical/chemical properties. We will assess drug loading, entrapment efficiency, stability, particle diameter, homogeneity and molecular weight. Afterwards, cytotoxicity against human GBM cells will be compared to normal human astrocytes. Because the scavenger receptor B type 1 (SR-B1) is known to interact with circulating HDL and the rHDL NPs, we will compare the cytotoxic efficiency of the drug transporting rHDL NPs against a high SR-B1 expressing GBM line (LN229) versus a low SR-B1 expressing GBM line (U87MG). SR-B1 levels will be assessed for all cell lines. Results: In this work we will demonstrate that after encapsulation of PI-103 into rHDL and characterization, we will observe cytotoxic effect against GBM cell lines, not normal astrocytes. Conclusion: If successful, future spheroid and mice studies, in addition to combination therapy studies, will advance the proof of concept of this therapy, allowing translation toward clinical applications.