Dendronized hyaluronic acid-docetaxel conjugate as a stimuli-responsive nano-agent for breast cancer therapy

To achieve target delivery of anti-tumor drugs with great biocompatibility into tumor tissues, a stimuli responsive dendronized hyaluronic acid (HA)-docetaxel conjugate (HA-DTX-Dendron, HADD) was designed and prepared. The incorporation of HA in HADD improved the delivery of DTX to tumor cells with rich CD44 receptors. Enhanced biocompatibility and therapeutic outcomes were achieved using glyodendrons-modified HA and tumor microenvironment-responsive linkers in HADD. The glycodendron was connected with HA via GSHresponsive disulfide bonds, and the drug DTX was linked to the carrier via a cathepsin B-responsive tetrapeptide GFLG. This design resulted in self-assembly nanostructures for facilitating uptake of HADD by tumor cells and rapid release of DTX to exert its therapeutic effect. Compared to free DTX, HADD showed much higher tumor growth inhibition in the MDA-MB-231 tumor-bearing mice model (up to 99.71%), and no toxicity was observed. Therefore, HADD could be employed as an efficacious nano-agent for treating triple negative breast cancer (TNBC).

Automated summary

A novel stimuli-responsive dendronized hyaluronic acid-docetaxel conjugate was designed to achieve targeted delivery of anti-tumor drugs with enhanced biocompatibility into tumor tissues. The design not only improved therapeutic outcomes but also reduced toxicity, making it an efficacious nano-agent for treating triple negative breast cancer.