Internalizing antibody-based targeted gene delivery for human cancer cells.
Gene therapy, a potential solution to hereditary and nonhereditary diseases, faces the challenges of safe and specific gene delivery. Cationic carrier molecules (e.g., liposome and polymers) that form noncovalent complexes with negatively charged DNA have been in use as nonviral gene delivery vectors. Although they tend to be relatively less efficient than viral systems, they have inherent advantages of flexibility and safety. Their derivatives, in conjugation with functional molecules such as peptides, proteins, growth factors, and antibodies, have been focused on to generate nanocarriers with low toxicity, high stability, high efficiency, and cell-specific targeting features. Here we describe internalizing polyclonal and monoclonal antibodies against a stress chaperone, mortalin/mtHsp70. We demonstrate that these internalizing anti-mortalin antibodies (i-mot Ab) could be employed for (1) internalization of nanoparticles (quantum dots, Qdots) and the generation of illuminating cells and (2) gene delivery. By using cancer and normal human cells in parallel, we further demonstrate that gene delivery can be specifically enhanced in human cancer cells if cationic polymer polyethylenimine (PEI) and i-mot Ab complex are used and may provide a novel cancer-targeting nanocarrier.
Shiota
Maki
M
National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8562, Japan.
Ikeda
Yutaka
Y
Kaul
Zeenia
Z
Itadani
Jun
J
Kaul
Sunil C
SC
Wadhwa
Renu
R
D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D018390:Gene Targeting / Q000379:methods*; D018014:Gene Transfer Techniques; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D011094:Polyethyleneimine
D000911:Antibodies, Monoclonal; D018840:HSP70 Heat-Shock Proteins; C080352:mortalin; D011094:Polyethyleneimine