Cellular association and cytotoxicity of doxorubicin-loaded immunoliposomes targeted via Fab' fragments of an anti-CD74 antibody.
The purpose of our research was to evaluate in vitro therapeutic efficacy of doxorubicin (DXR)-loaded immunoliposomes with Fab' fragments of the anti-CD74 antibody LL1 attached to the surface. LL1 is well suited for targeting purposes because it is internalized very fast by B-lymphoma cells. However, at in vivo application whole antibodies show fast clearance in circulation. Taking this fact into consideration, this study was initiated to elucidate the prospects of using Fab' fragments of LL1 in stead of the whole antibody for future targeting in vivo of DXR-loaded liposomes. The Fab' fragments were covalently attached to the surface of sterically stabilized liposomes by use of a PEG-based heterobifunctinal coupling agent. LL1 Fab' conjugated sterically stabilized DXR liposomes showed approximately six times faster accumulation of the drug in Raji human B-lymphoma cells than nontargeted liposomes. In vitro cytotoxicity, quantitated by a tetrazolium assay, against Raji cells gave IC(50) values of 0.13, 0.45, and 0.11 microM for DXR-loaded immunoliposomes, DXR-loaded liposomes and free drug, respectively. The results from this study suggest that DXR-loaded immunoliposomes targeted with Fab' fragments from the anti-CD74 antibody LL1 could be a useful system for future in vivo experiments.
Lundberg
B B
BB
Department of Biochemistry and Pharmacy, Abo Akademi University, Abo, Finland. bolundbe@abo.fi
Griffiths
G
G
Hansen
H J
HJ
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005079:Excipients; D000949:Histocompatibility Antigens Class II / Q000737:chemistry*; D007120:Immunochemistry; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000737:chemistry; D007700:Kinetics; D008081:Liposomes
D000903:Antibiotics, Antineoplastic; D000944:Antigens, Differentiation, B-Lymphocyte; D005079:Excipients; D000949:Histocompatibility Antigens Class II; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D008081:Liposomes; C045084:invariant chain; D004317:Doxorubicin