Targeting immunoliposomes to pulmonary type II and tracheobroncheal epithelial cells

Specific agents are necessary to target therapies to certain cell types, bo th to maximize benefit and to minimize damage to healthy cells. Immunolipos omes (IL) may help to target the delivery of therapeutic drugs and DNA mole cules to specific cells or organs. We describe here the characterization in vitro of an immunoliposome incorporating A2R, a monoclonal antibody that r ecognizes a receptor for surfactant protein-A (SP-A) present on both type I I pneumocytes and the epithelium of the conducting airways. A2R-immuno-lipo somes (A2R-IL) containing beta-galactosidase as a marker were prepared by c oupling derivatized A2R to Liposomes made of phosphatidylcholine and choles terol. Control IL were prepared similarly, but incorporated normal IgG inst ead of A2R (IgG-IL), or no Ig (Null-IL). Type IT cells in primary explant c ell culture were treated with either A2R-IL, IgG-IL, or null-IL. We found h ighly significant differences in binding between specific and nonspecific I L: 31.44% of type II cells incubated with A2R-IL showed transfer of the bet a-gal. Pretreatment of the type II cells with SP-A blocked SP-A receptors a nd reduced the uptake of A2R-IL almost to background levels. As SP-A recept or is present on the cells of the conducting airways, we tested tracheal ex plants for their ability to take up A2R-IL, and found that these cells, sim ilarly, could be targeted by A2R-IL. Thus, this immunoliposome could facili tate future study and therapies directed at type II alveolar cells and/or t racheobroncheal epithelium.