DataSheet_1_Locally Controlled Release of Methotrexate and Alendronate by Thermo-Sensitive Hydrogels for Synergistic Inhibition of Osteosarcoma Progression.docx

Osteosarcoma (OS) is a serious primary bone malignant tumor that can easily affect children and adolescents. Chemotherapy is one of the important and feasible clinical treatment strategies for the treatment of OS at present, which is severely limited due to insufficient retention time, poor penetration ability, and serious side effects of current anti-tumor drug preparations. In this work, a novel injectable thermo-sensitive hydrogel (mPEG45–PLV19) loaded with methotrexate and alendronate, and the sustained release at the tumor site synergistically inhibited the progression of OS. The mPEG45–PLV19 shows excellent physical and chemical properties. Compared with other treatment groups, the in vivo treatment of gel+ methotrexate + alendronate effectively inhibited the growth of tumor. More importantly, it significantly reduced bone destruction and lung metastasis caused by OS. Therefore, this injectable thermo-sensitive hydrogel drug delivery system has broad prospects for OS chemotherapy.

骨肉瘤（OS）是一种严重原发性骨恶性肿瘤，易于影响儿童及青少年。化疗是目前治疗骨肉瘤的重要且可行的临床治疗策略之一，然而，由于当前抗肿瘤药物制剂的药物滞留时间不足、渗透能力差以及严重的副作用，其应用受到极大限制。在本研究中，我们开发了一种新型可注射型温敏水凝胶（mPEG45–PLV19），其中负载了甲氨蝶呤和依替膦酸二钠，并在肿瘤部位实现持续释放，协同抑制了骨肉瘤的进展。mPEG45–PLV19水凝胶展现出优异的物理和化学性质。与其它治疗组相比，凝胶+甲氨蝶呤+依替膦酸二钠的体内治疗有效抑制了肿瘤的生长。更重要的是，它显著减少了由骨肉瘤引起的骨破坏和肺转移。因此，这种可注射型温敏水凝胶药物递送系统在骨肉瘤化疗中具有广阔的应用前景。