JOURNAL OF LIPOSOME RESEARCH, 9(2), 199-228 (1999) zyxw CELLULAR TRAFFICKING AND CYTOTOXICITY DOXORUBICIN IN B LYMPHOMA CELLS? OF ANTI-CD19-TARGETED LIPOSOMAL Daniel E. Lopes de Menezes,a Marc J. Kirchmeier,a Jean-Francois Gagne,aLinda M. Pilarski,hand Theresa M. Allen'* 'Department of Pharmacology, University of Alberta, Edmonton, Alberta T6G 2H7 and bDepartment of Oncology, Cross Cancer Institute, Edmonton, Alberta T6G 122 ABSTRACT We have previously demonstrated that liposomal doxorubicin (DXR), targeted against the CD19 receptor of human B lymphoma (Namalwa) cells resulted in selective affinity of SIL[anti-CD19] for CD19+ Namalwa cells zy in zyx vitro and significantly increased therapeutic efficacy in mice compared to non- targeted liposomal DXR or to free drug (1). In this study we have examined the cellular trafficking of DXR in Namalwa cells for free drug compared to non-targeted liposomal drug (DXR-SL) or immunoliposomal drug targeted via the monoclonal antibody anti-CD19 (DXR-SIL[anti-CDl9]). Liposomes were sterically stabilized with lipid derivatives of polyethylene glycol (PEG) and anti-CD19 was attached to the PEG terminus. Time-dependent studies using flow cytometry revealed that free DXR accumulated rapidly in cells. Drug from DXR-SIL[anti-CD19] accumulated less rapidly in Namalwa cells than free drug but the cellular levels of DXR were several-fold higher than for drug presented in non-targeted DXR-SL. Internalization of SIL[anti-CD 191 into a low pH compartment could be demonstrated using a pH-sensitive probe, ?This paper has been submitted for The Demetrios Papahadjopoulos Young Investigator's Award. *Corresponding Author: Departments of Pharmacology, University of Alberta, Edmon- ton, AB. T6G 2H7. Tel.: (780) 492-5710; Fax: (780) 492-8078; or E-mail: terry.allen@ ualberta.ca 199 Copyright zyxwvuts 0 1999 by Marcel Dekker, Inc. www.dekker.com Journal of Liposome Research Downloaded from informahealthcare.com by University of Alberta on 12/24/14 For personal use only.