Nanoliposome-mediated targeting of antibodies to tumors: IVIG antibodies as a model

Abstract

Monoclonal antibodies are routinely used as tools in immunotherapies against solid tumors. However, administration of monoclonal antibodies may cause undesired side effects due to their accumulation in non-targeted organs. Nanoliposomes of less than 200nm can target antibodies to tumors by enhanced permeation and retention (EPR) mechanisms. To direct monoclonal antibodies to tumors, nanoliposomes encapsulating intravenous immunoglobulin (IVIG) as a model antibody were prepared. The liposomes had average diameters of 100nm and encapsulation efficiencies of 31 to 46%. They showed less than 10% release in plasma at 37°C up to seven days. The secondary and tertiary structures of liposome-encapsulated antibodies were analyzed by circular dichroism (CD) spectroscopy. The near and far-UV spectra analyses revealed no obvious conformational changes in the structures of the encapsulated antibodies. The biodistribution of free and liposome-encapsulated iodinated antibodies was investigated in mice bearing C-26 colon carcinoma tumors. The accumulation of liposome-encapsulated antibodies in tumors was significantly greater than that of free antibodies due to the EPR effect. The PEGylated liposomes were more efficient in the delivery of antibodies to the tumor site than non-PEGylated liposomes. We conclude that administration of monoclonal antibodies in PEGylated liposomes is more efficient than administration of non-encapsulated monoclonal antibodies for solid tumor immunotherapy.