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. The gene discussed is HPSE; the disease is neoplasm.