HPSE and osteosarcoma: Huang et al. (2019) developed an enzyme-responsive nanoparticle, namely paclitaxel (PTX)-DOTAP@alloferon-1-heparin/protamine, for the treatment of tumors expressing high levels of heparanase-1, a characteristic feature of highly metastatic osteosarcoma. The outer layer of this nanosystem was designed to disassemble upon the degradation of heparin by the extracellular matrix’s highly expressed heparanase-1, thereby releasing PTX and protamine for effective tumor therapy. In vitro and in vivo experiments confirmed the efficacy of this nanosystem in the treatment of osteosarcoma.