Hyaluronan like polysaccharide based nanodrugs with enhanced CD44 avidity for image-guided drug delivery to breast cancer

Abstract

Targeted drug delivery is an exciting strategy to treat cancer and reduce the harmful side effects of chemotherapy to normal tissues. CD44 has been an attractive target for drug delivery due to its expression on many types of tumor cells including breast cancer. To better target the CD44-expressing breast cancer cells, we report the design and synthesis of a new nanodrug, G2-Sal-ICG, comprising a hyaluronan (HA)-like polysaccharide (G2) conjugated with the anticancer drug salinomycin (Sal) and the imaging agent indocyanine green (ICG). This nanodrug targets CD44 receptors and allows for near-infrared fluorescence imaging (NIR-FI) to track drug delivery in real-time. G2-Sal-ICG had significantly higher affinity with CD44⁺ cancer cells than the corresponding nanodrug of unmodified HA conjugated with Sal and ICG (HA-Sal-ICG). In vitro studies demonstrated that the nanodrug can be released in typical lysosomal conditions, leading to effective cancer cell killing. In vivo experiments with an orthotopic breast cancer model demonstrated the superior tumor-targeting capability of G2-Sal-ICG and its ability to significantly suppress tumor growth. Our findings suggested G2-Sal-ICG is a promising theranostic nanodrug for CD44-targeted therapy, combining efficient drug delivery with real-time non-invasive imaging, thus highlighting its potential for clinical applications in breast cancer treatment.