Tumor stromal cells have been recently recognized to contribute to
tumor growth. Therefore, we hypothesized that delivery of anticancer drugs to these cells in addition to the
tumor cells might treat
cancer more effectively. Stromal cells abundantly expressed
Platelet-Derived Growth Factor Receptor-
beta (PDGFR-beta) in different human
tumors as shown with immunohistochemistry. To achieve targeting through
PDGFR-beta, we developed a carrier by modifying
albumin with a
PDGFR-beta recognizing
cyclic peptide (pPB-HSA). pPB-HSA specifically bound to
PDGFR-beta-expressing 3T3 fibroblasts, C26 and A2780
cancer cells in vitro. Subsequently,
doxorubicin was conjugated to pPB-HSA through an
acid-sensitive
hydrazone linkage. In vitro, Dox-HSA-pPB was taken up by fibroblasts and
tumor cells and a short exposure of the conjugate induced cell death in these cells. In vivo, the conjugate rapidly accumulated into
PDGFR-beta expressing cells in C26
tumors. Treatment with Dox-HSA-pPB significantly reduced the C26
tumor growth in mice while free
doxorubicin treated mice had lower response to the
therapy. Furthermore, in contrast to free
doxorubicin the conjugate did not induce loss in
body weight. In conclusion, the present study reveals a novel approach to target key cell types in
tumors through
PDGFR-beta, which can be applied to enhance the therapeutic efficacy of anticancer drugs.