Heparanase-responsive nanomaterial for anaplastic thyroid cancer chemotherapy

Anaplastic thyroid cancer (ATC) is aggressive and has a high mortality rate. Doxorubicin (DOX), the first-line chemotherapy drug for ATC, has an insufficient effective concentration and severe cardiac toxicity, limiting its clinical application. Therefore, it is urgent to enhance efficacy of DOX and reduce its toxicity. Designing stimulus-responsive drug delivery systems (DDSs) based on the characteristics of the tumor microenvironment may be a promising approach for the treatment of ATC. We found that heparanase (HPSE) is highly expressed in the tumor microenvironment of ATC but not in normal thyroid tissue. In this study, we successfully constructed and characterized the HPSE-responsive self-assembled carrier TET-HS-NI, which was modified with 3,3,5,5-Tetraiodothyroacetic acid (TET) that targetsαvβ3. DOX was loaded into TET-HS-NI to construct TET-HS-NI/DOX. The zebrafish cell-derived xenograft (CDX) and ATC orthotopic models showed that TET-HS-NI/DOX significantly improved the antitumor efficacy and safety of DOX. In a word , we have constructed a drug delivery system sensitively released DOX in the ATC environment where HPSE overexpressed, increasing the effective concentration at the tumor site and provide a new method for the treatment of ATC.