Fig. 1.

Schematic drawing of Polycefin. This delivery device was used for inhibiting the expression of laminin α4 and β1 chains by morpholino AONs in vitro and in vivo to prevent angiogenesis of glial tumors. The modules are (1) morpholino AON 1a (to α4 chain) and 1b (to β1 chain) conjugated to the scaffold by disulfide bonds, which are cleaved in the cytoplasm by glutathi-one to release the free drugs, (2) mAb to transferrin receptor for cancer cell targeting and receptor-mediated endocytosis, (3) PEG for protection, (4) stretches of conjugated L-valine to provide pH-dependent lipophilicity for the disruption of endosomal membranes, and (5) optional fluorescent reporter dye (Fluorescein or Alexa Fluor 680) for detection