Doxorubicin-encapsulating liposomal formulations, known as
Doxil, have been used for the treatment of
Kaposi's sarcoma and
ovarian cancer. However, there is still a need for a drug delivery system for
doxorubicin that limits the treatment's side effects, namely,
mucositis and hand-and-foot syndrome. The AG73
peptide derived from the
laminin α1 chain is a
ligand for
syndecans, and
syndecan-2 is highly expressed in some
cancer cells. In this study, to develop a safer and more selective liposomal formulation, we prepared
doxorubicin-encapsulating AG73
peptide-modified
liposomes (AG73-Dox). First, we assessed the selectivity of AG73-Dox for
cancer cells, including
syndecan-2 over-expressing cells, using flow cytometry and confocal microscopy. AG73-Dox showed selective cellular uptake on
cancer cells and enhancement of the intracellular uptake. Next, we examined the cytotoxicity of AG73-Dox using a WST assay. AG73-Dox exhibited a higher cytotoxicity against
cancer cells than other control
liposomes. In addition, we showed that the antitumor efficacy of AG73-Dox in vivo was better than that of free Dox. When we examined the biodistribution of
liposomes, AG73
peptide-modified
liposomes (AG73-L) tended to bind to intratumoral vessels and extravasated in the
tumor tissue. Thus, further optimization of AG73-L toward
tumor targeting may lead to a development of a useful tool for
cancer therapy.