Dual-modal imaging-guided theranostic nanocarriers based on 2-methoxyestradiol and indocyanine green

Drug toxicity and insufficient drug dosing place a limit on the effect of chemotherapy. Optimal efficacy is achieved by exposing tumor cells to the maximum tolerated dose of a chemotherapeutic drug. In this study, we developed a strategy (graphic summary) for enhancing the therapeutic and diagnostic capabilities of known chemotherapeutics. We used a dual-mode near-infrared (NIR) fluorescence/photoacoustic imaging technology to achieve actively guided tumor targeting of the photothermal therapeutic agent indocyanine green (ICG) and the chemotherapeutic drug 2-methoxyestradiol (2-ME), which were loaded into thermosensitive liposomes (TSLs) with surface-grafted tumor-targeting peptide cRGDyk (cRGDyk-2-ME@ICG-TSLs). In vitro studies demonstrated that cRGDyk-2-ME@ICG-TSLs effectively induced drug accumulation and cytotoxicity in NIR laser-irradiated B16-F10 melanoma cells using dual targeting based on the cRGDyk peptide and temperature sensitivity. An in vivo study showed that 24 h after intravenously injecting cRGDyk-2-ME@ICG-TSLs into melanoma tumor-bearing mice, the dual-mode NIR fluorescence/photoacoustic imaging could accurately identify tumors and normal tissues. In addition, the combination of cRGDyk-2-ME@ICG-TSLs and NIR radiation suppressed tumor growth in tumor-bearing nude mice and was associated with a low risk of side effects on normal organs. Our results indicate that TSLs are a suitable drug delivery system for diagnostic and chemotherapeutic agents guided by dual-mode imaging.