Tumor-targeted liposomes: doxorubicin-loaded long-circulating liposomes modified with anti-cancer antibody.
Commercially available doxorubicin-loaded long-circulating liposomes (Doxil, Alza Pharmaceuticals) were modified with the monoclonal nucleosome (NS)-specific 2C5 antibody (mAb 2C5) that recognizes a broad variety of tumors via the tumor cell surface-bound NSs. For incorporation into liposomes, mAb 2C5 was modified with poly(ethylene glycol)-phosphatidyl ethanolamine conjugate (PEG-PE) with the free PEG terminus activated with the p-nitrophenylcarbonyl group (pNP-PEG-PE). Derivatives of mAb 2C5 containing a variable number of PEG-PE residues (10-32) per protein molecule were prepared with a reasonably good preservation of the antibody specific activity even at the highest degree of modification. PEG-PE-modified antibody quantitatively incorporated into the liposomal membrane of doxorubicin-loaded liposomes with a loss of not more than 20% of the encapsulated doxorubicin. 2C5-targeted Doxil liposomes acquired the ability to recognize NSs and specifically bind to various tumor cells. Doxorubicin-loaded long-circulating liposomes modified with the mAb 2C5 kill various tumor cells in vitro with the efficiency higher than non-targeted doxorubicin-loaded liposomes.
Lukyanov
Anatoly N
AN
Department of Pharmaceutical Sciences, Bouve College of Health Sciences, Northeastern University, Mugar Bldg 312, 360 Huntington Aveneu, Boston, MA 02115, USA.
Elbayoumi
Tamer A
TA
Chakilam
Ananthsrinivas R
AR
Torchilin
Vladimir P
VP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage*; D006801:Humans; D008081:Liposomes; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D009707:Nucleosomes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D008081:Liposomes; D009707:Nucleosomes; D004317:Doxorubicin