S-trans-trans-Farnesylthiosalicylic acid (FTS) is a Ras inhibitor that exhibits desirable anticancer property and currently undergoing clinical trials for
pancreatic cancer (PC). However, its poor water solubility and low bioavailability have severely hampered clinical applications. A strategy to improve FTS bioavailability is to develop a suitable
drug delivery method. Here, we use a near-infrared fluorescence (NIRF) heptamethine
carbocyanine (HC)
dye conjugated with FTS (to produce FTS-148) as a drug delivery system to enhance FTS bioavailability. We further investigate its
tumor-targeting functions. FTS-148 displayed better bioavailability and photophysical property and selective recognition of
cancer cells. FTS-148 significantly reduced PC cell proliferation, and more effective than FTS in restricting
tumor growth both in a cell-derived xenograft (CDX) model and a patient-derived
tumor xenograft (PDX) model. FTS-148 can specifically recognize PC cells in mice subcutaneous models or rabbit orthotopic models and allows real-time monitoring of the
therapeutic effects by NIRF optical imaging. FTS-148 treatment significantly reduced Ras expression in PC cells and increased
tumor tissue apoptosis. In short, FTS conjugated with HC
dye had enhanced bioavailability and
tumor-targeting property. It provides a potential agent for imaging and
therapy of PC.