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Updated: May 7, 2026
Study of Phagolysosome Biogenesis in Live Macrophages
Published on: March 10, 2014
Translational studies of phenotypic probes for the mononuclear phagocyte system and liposomal pharmacology
Whitney P Caron1, John C Lay, Alan M Fong
1Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy (W.P.C., P.K., S.E.N., W.C.Z.), School of Medicine (J.C.L., A.M.F., D.L.C.-P., W.R.B., L.V.L., V.L.B.-J., P.A.G.), Department of Biostatistics (H.Z., J.H.M.), Lineberger Comprehensive Cancer Center (D.L.C.-P., W.R.B., L.V.L., V.L.B.-J., P.A.G., W.C.Z.), Institute for Pharmacogenomics and Individualized Therapy (W.C.Z.), Carolina Center of Cancer Nanotechnology Excellence (W.C.Z.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; School of Pharmacy, Texas Tech University Health Sciences Center, St. Amarillo, Texas (N.M.L.-B.); and North Carolina Biomedical Innovation Network, Research Triangle Park, North Carolina (W.C.Z.).
Abstract:
As nanoparticles (NPs) are cleared via phagocytes of the mononuclear phagocyte system (MPS), we hypothesized that the function of circulating monocytes and dendritic cells (MO/DC) in blood can predict NP clearance (CL). We measured MO/DC phagocytosis and reactive oxygen species (ROS) production in mice, rats, dogs, and patients with refractory solid tumors. Pharmacokinetic studies of polyethylene glycol (PEG)-encapsulated liposomal doxorubicin (PEGylated liposomal doxirubicin [PLD]), CKD-602 (S-CKD602), and cisplatin (SPI-077) were performed at the maximum tolerated dose. MO/DC function was also evaluated in patients with recurrent epithelial ovarian cancer (EOC) administered PLD. Across species, a positive association was observed between cell function and CL of PEGylated liposomes. In patients with EOC, associations were observed between PLD CL and phagocytosis (R(2) = 0.43, P = 0.04) and ROS production (R(2) = 0.61, P = 0.008) in blood MO/DC. These findings suggest that probes of MPS function may help predict PEGylated liposome CL across species and PLD CL in patients with EOC.
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