Antibody-Mediated Targeting of Long-Circulating (Stealth^R) Liposomes

Abstract

Long-circulating or Stealth^R liposomes (S-liposomes) have a number of important properties which make them good candidates for targeting applications. These include long circulation half-lives, dose-independent pharmacokinetics and ability to move through the lymph after subcutaneous injection. A number of techniques are available for attaching antibodies to the surface of S-liposomes. S-liposomes retain their prolonged circulation times in the presence of bound antibody. In the case of liposomes containing polyethylene glycol-lipid derivatives, the ability of bound antibody to recognize its target is dependent on the molecular weight of polyethylene glycol contained in the liposomes. Antibody-mediated specific binding of S-liposomes to cells in culture could be demonstrated, as well as increased cytotoxicity in vitro of targeted S-liposomes containing anticancer drugs. Targeting of antibody-containing S-liposomes could also be demonstrated in vivo. In one therapeutic application, dramatic increases in survival rate could be demonstrated in mice bearing lung squamous cell carcinoma following treatment with doxorubicin entrapped in S-liposomes with attached monoclonal antibody.