Preclinical evaluation and monitoring of the therapeutic response of a dual targeted hyaluronic acid nanodrug

Abstract

Chemotherapy is a powerful cancer treatment but suffers from poor biocompatibility and a lack of tumor targeting. Here, we developed a CD44-targeted polymeric nanocomplex by encapsulating 10-hydroxycamptothecin (HCPT) into hyaluronic acid nanoparticles (HANP) for targeted cancer therapy. In vitro, theHANP/HCPT showed improved cytotoxicity to five cancer cell lines including HT29, A549,MDA-MB-231,HepG2, andMDA-MB-435 versus freeHCPT.After systemic administration into MDA-MB- 231 breast cancer xenograft, tumor growth was significantly inhibited 5.25 ± 0.21 times in the HANP/HCPT treated group relative to the nontreated group. In addition, the treatment response was also accessed and confirmed by 18F-fluoro-2-deoxy-D-glucose ([18F] FDG) positron emission tomography (PET). The MDA-MB-231 tumors responded to HANP/HCPT 7 days after the first treatment, which benefits treatment strategy adjustment and personalization. No apparent systemic toxic effects were seen in mice treated with HANP/HCPT. In summary, the HANPs have great promise as a targeted drug carrier for cancer chemotherapy. Our HANP platform can also deliver other hydrophobic chemotherapy agents.