The efficacy of drug delivery systems can be significantly enhanced by making them target-specific via the attachment of various
ligands to their surface. We attempted to enhance
tumor accumulation and
therapeutic effect of
doxorubicin-loaded long-circulating
liposomes (
Doxil, ALZA Corp.) by coupling to their surface the anticancer
monoclonal antibody 2C5 (mAb 2C5) with nuclesome (NS)-restricted activity, that can recognize the surface of various
tumor but not normal cells via the surface-bound
nucleosomes released from the apoptotically dying neighboring
tumor cells and specifically targets
pharmaceutical carriers to
tumor cells in vitro and in vivo. Antibody coupling to PEGylated
doxorubicin-
liposomes was performed by the "post-insertion" technique. The pharmacokinetics of plain and immuno-targeted
Doxil-mimicking
liposomes, as well as their accumulation in primary
Lewis lung carcinoma (LLC)
tumors in mice was followed by real-time gamma-scintigraphy upon liposomal membrane labeling with (111)In. Therapeutic action of various liposomal formulations was followed by registering primary
tumor growth, determining
tumor weigh upon mice sacrifice, and by counting the number of
metastases in the liver and lungs. 2C5 antibody-targeted
liposomes demonstrate significantly enhanced accumulation in LLC
tumors. Targeted
doxorubicin-loaded PEG-
liposomes were significantly more effective in inhibiting
tumor growth and metastatic process in the LLC
tumor models in mice. Our results clearly show the remarkable capability of 2C5-targeted
Doxil to specifically deliver its cargo into various
tumor manifestations (solid and metastatic) significantly increasing the efficacy of
therapy.