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Targeting Human Brain Tumor with Anti-Nucleosome Antibody 2C5-modified Liposomes in Nude Mice Model

B. Gupta, T.S. Levchenko, D.A. Mongayt and V.P. Torchilin
Northeastern University, US

Keywords:
brain tumor, U-87 MG, targeting, immunoliposomes, nude mice

Abstract:
Delivery systems such as liposomes have shown promising potential to overcome the existing brain barriers and deliver the anti-cancer drugs in therapeutic amounts to brain tumors. Further modification of liposomes with monoclonal antibodies enhances their ability to target the desired area. Previous studies have shown the potential of monoclonal antibody 2C5 (mAb 2C5), an anti-nucleosome antibody, to target nanocarriers such as micelles and liposomes to a variety of tumors. We hypothesized that mAb 2C5 can be used for the targeted delivery of doxorubicin-loaded liposomes to brain tumors in vivo. The cytotoxicity studies with 2C5-modified Doxil® (a commercial preparation of liposomal doxorubicin) demonstrated the ability of mAb 2C5 to target the liposomes and deliver anti-cancer agent doxorubicin within U-87 MG brain tumor cells to achieve cell death at a lower dose of doxorubicin. The therapeutic treatment studies on intracranial tumor model in nude mice showed that 2C5-Doxil® was significantly effective in inhibiting the tumor growth and hence prolonging the survival time of the tumor-bearing mice over control liposomes. We therefore concluded that 2C5-modified long circulating immunoliposomes can potentially be considered for the delivery of anti-cancer agents, and hence for the therapeutic treatment of human brain tumors in vivo.

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