Targeting of Drugs to Solid Tumors Using Anti-Her2 Immunoliposomes

• Published in: Journal of liposome research 1998-01, Vol.8 (4), p.425-442
• Main Authors: Papahadjopoulos, Demetrios, Kirpotin, Dmitri B., Park, John W., Hong, Keelung, Shao, Yi, Shalaby, Refaat, Colbern, Gail, Benz, Christopher C.
• Format: Article
• Language: English
• ISSN: 0898-2104; 1532-2394
• DOI: 10.3109/08982109809039930

Abstract Cancer therapy would clearly benefit from a carrier system capable of intracellular delivery of systemically administered drugs to cancer cells in solid tumors. Sterically stabilized immunoliposomes specific to the cells expressing HER2 protooncogene (anti-HER2 SIL), were designed by conjugating Fab' fragments of a recombinant humanized anti-HER2 MAb to the distal termini of poly(ethylene glycol) chains on the surface of unilamellar liposomes (size 90-100 nm) of phosphatidylcholine, cholesterol, and poly (ethylene glycol)-derivatized phosphatidylethanolamine. Anti-HER2 SIL avidly and specifically bound to cultured HER2-overexpressing cancer cells (8,000-23,000 vesicles per cell) and became endocytosed (ke = 0.022-0.033 min.−1) via the coated pit pathway. Anti-HER2 SIL showed prolonged circulation lifetime in rats (blood MRT approx. 24 hours) and significantly increased antitumor activity of encapsulated doxorubicin against HER2-overexpressing human breast cancer xenografts in nude mice. Although the accumulation of anti-HER2 SIL in HER2-overexpressing tumor xenografts was not increased over that of non-targeted sterically stabilized liposomes (SL), microscopic examination revealed abundance of anti-HER2 SIL in the interstitial spaces, as well as within the cytoplasm of cancer cells, while identical liposomes lacking anti-HER2 Fab' were located predominantly within tumor-resident macrophages. Anti-HER2 SIL, a targeted vehicle capable of in vivo intracellular delivery of substances to HER2-overexpressing solid cancers, enhances the potential for tumor targeting and opens new avenues for better treatment of cancer.