Dual-Modal Imaging-Guided Theranostic Nanocarriers Based on 2-Methoxyestradiol and Indocyanine Green

Abstract

The effect of a chemotherapeutic drug is always limited by insufficient drug dose and drug toxicity. However, when tumor cells are exposed to the maximum concentration of a chemotherapeutic drug, the best effect can be achieved. Here we developed a strategy (graphic summary) to enhance the therapeutic and diagnostic capabilities of known chemotherapeutics. We used a dual-mode near-infrared (NIR) fluorescence/photoacoustic imaging technology to actively guide the photothermal therapeutic agent indocyanine green (ICG) and a chemotherapeutic drug 2-methoxyestradiol (2-ME) loaded into thermosensitive liposomes (TSLs), on the surfaces of which was grafted the tumor-targeting peptide cRGDyk, (cRGDyk-2-ME@ICG-TSL) to the tumor target. Drug release studies have shown that TSL has a satisfactory performance for targeting and releasing 2-ME under the high temperature conditions induced by NIR laser irradiation. In vitro studies confirmed that cRGDyk-2-ME@ICG-TSLs can effectively induce drug accumulation and cytotoxicity in B16-F10 melanoma cells under near-infrared laser irradiation using cRGDyk peptide and temperature-sensitive dual targeting. Twenty-four hours after the intravenous injection of cRGDyk-2-ME@ICG-TSLs into melanoma tumor-bearing mice, 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 nude mice bearing tumors and was associated with a lower risk of side effects on normal organs. Our results indicate that TSLs can increase the therapeutic index of chemotherapeutic drugs and is suitable as a drug delivery system for diagnostic and tumor treatment tools guided by dual-mode imaging.