Enhanced antitumor efficacy of folate‐linked liposomal doxorubicin with TGF‐β type I receptor inhibitor

Tumor cell targeting of drug carriers is a promising strategy and uses the attachment of various ligands to enhance the therapeutic potential of chemotherapy agents. Folic acid is a high‐affinity ligand for folate receptor, which is a functional tumor‐specific receptor. The transforming growth factor (TGF)‐β type I receptor (TβR‐I) inhibitor A‐83‐01 was expected to enhance the accumulation of nanocarriers in tumors by changing the microvascular environment. To enhance the therapeutic effect of folate‐linked liposomal doxorubicin (F‐SL), we co‐administrated F‐SL with A‐83‐01. Intraperitoneally injected A‐83‐01‐induced alterations in the cancer‐associated neovasculature were examined by magnetic resonance imaging (MRI) and histological analysis. The targeting efficacy of single intravenous injections of F‐SL combined with A‐83‐01 was evaluated by measurement of the biodistribution and the antitumor effect in mice bearing murine lung carcinoma M109. A‐83‐01 temporarily changed the tumor vasculature around 3 h post injection. A‐83‐01 induced 1.7‐fold higher drug accumulation of F‐SL in the tumor than liposome alone at 24 h post injection. Moreover F‐SL co‐administrated with A‐83‐01 showed significantly greater antitumor activity than F‐SL alone. This study shows that co‐administration of TβR‐I inhibitor will open a new strategy for the use of FR‐targeting nanocarriers for cancer treatment. ( Cancer Sci 2010); 00: 000–000