Tumor targeting of vincristine by mBAFF-modified PEG liposomes in B lymphoma cells.
Malignant hematologic diseases are highly malignant and refractory to conventional therapies. Ligand-mediated targeting of liposomal anticancer drugs to surface receptors expressed on malignant B cells can be an effective strategy for treating B-cell malignancies. BAFF plays an important role in the maintenance of normal B-cell development and homeostasis and the expression of its receptors is significantly increased in numerous B-cell malignancies. mBAFF (a soluble BAFF mutant with amino acid 217-224 being replaced by two glycine residues) may be used as a competitive inhibitor for BAFF to treat relevant malignant hematologic diseases. It may also hold promise as a novel ligand for targeted anticancer therapy. In this study, we show that liposomes that are sterically stabilized by PEG and surface decorated with mBAFF exhibited strong affinity and specificity to cultured human Raji B lymphoma cells. Vincristine formulated in the targeted liposomes showed significantly higher levels of cytotoxicity towards Raji cells than the nontargeted liposomal drug. Therapeutic experiments in SCID mice implanted with Raji cells showed significantly prolonged survival time with targeted liposomal vincristine compared to either free VCR or vincristine formulated in nontargeted liposomes. These studies suggest the potential of the mBAFF-modified liposomal drugs in targeted therapy of B-cell malignancies.
Zhang
Li
L
Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, PR China.
Gao
Huiguang
H
Chen
Linfeng
L
Wu
Bo
B
Zheng
Yingru
Y
Liao
Rongxia
R
Jiang
Yu
Y
He
Fengtian
F
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D053264:B-Cell Activating Factor / Q000008:administration & dosage*; D005260:Female; D008081:Liposomes; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D011092:Polyethylene Glycols / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage*
D000972:Antineoplastic Agents, Phytogenic; D053264:B-Cell Activating Factor; D008081:Liposomes; C505720:Tnfsf13b protein, mouse; D011092:Polyethylene Glycols; D014750:Vincristine