Preclinical Evaluation and Monitoring of the Therapeutic Response of a Dual Targeted Hyaluronic Acid Nanodrug

Abstract EN

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, the HANP/HCPT showed improved cytotoxicity to five cancer cell lines including HT29, A549, MDA-MB-231, HepG2, and MDA-MB-435 versus free HCPT.

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.