title: Profiling the relationship between tumor-associated macrophages and pharmacokinetics of liposomal agents in preclinical murine models.
abstract: The mononuclear phagocyte system (MPS) has previously been shown to significantly affect the clearance, tumor delivery, and efficacy of nanoparticles (NPs). This study profiled MPS cell infiltration in murine preclinical tumor models and evaluated how these differences may affect tumor disposition of PEGylated liposomal doxorubicin (PLD) in models sensitive and resistant to PLD. Significant differences in MPS presence existed between tumor types (e.g. ovarian versus endometrial), cell lines within the same tumor type, and location of tumor implantation (i.e. flank versus orthotopic xenografts). Further, the differences in MPS presence of SKOV-3 ovarian and HEC1A endometrial orthotopic cancer models may account for the 2.6-fold greater PLD tumor exposure in SKOV-3, despite similar plasma, liver and spleen exposures. These findings suggest that profiling the presence of MPS cells within and between tumor types is important in tumor model selection and in tumor types and patients likely to respond to NP treatment.
authors.affiliation: Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Lucas
authors.affiliation: UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
authors.forename: Taylor F
authors.initials: TF
authors.lastname: White
authors.affiliation: Lineberger Comprehensive Cancer Center Biostatistics Core, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Deal
authors.affiliation: UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
authors.forename: Leah B
authors.initials: LB
authors.lastname: Herity
authors.affiliation: Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Gina
authors.initials: G
authors.lastname: Song
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; The Animal Studies Core, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Charlene M
authors.initials: CM
authors.lastname: Santos
authors.affiliation: Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: zamboni@email.unc.edu.
authors.forename: William C
authors.initials: WC
authors.lastname: Zamboni
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D008954:Models, Biological; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010743:Phospholipids / Q000627:therapeutic use; D011092:Polyethylene Glycols
chemical_list: D000903:Antibiotics, Antineoplastic; D010743:Phospholipids; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Mononuclear phagocyte system; Nanoparticles; PEGylated liposomal doxorubicin; Preclinical cancer models; Tumor-associated macrophages