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Local delivery of sunitinib and Ce6 via redox-responsive zwitterionic hydrogels effectively prevents osteosarcoma recurrence.
Journal of Materials Chemistry B ( IF 7 ) Pub Date : 2020-06-04 , DOI: 10.1039/d0tb00970a
Zhaolong Yu 1 , Zecong Xiao 2 , Xintao Shuai 2 , Jiwei Tian 1
Affiliation  

Surgery combined with adjuvant or neoadjuvant chemotherapy is still the standard treatment for osteosarcoma. However, the high risk of tumor recurrence and side effects of chemotherapy usually lead to high mortality for cancer patients. Herein, the multi-targeted receptor tyrosine kinase (RTK) inhibitor sunitinib (Sun) and photodynamic therapy (PDT) drug chlorin e6 (Ce6) were locally delivered to the postoperative tumor site via a zwitterionic hydrogel. This hydrogel exhibited excellent biocompatibility and redox responsiveness. In vitro study demonstrated that Sun/Ce6@Gel induced 143B human osteosarcoma cell apoptosis via downregulating the expression of Bcl-2 and upregulating the expression levels of Bax and caspase-3. Similarly, the in vivo study showed that Sun/Ce6@Gel provided sustained drug release under redox conditions, and then synergistically induced tumor apoptosis to prevent tumor recurrence without systemic toxicity. Therefore, local implantation of Sun/Ce6@Gel may be a promising topical therapeutic method for prevention of the recurrence of osteosarcoma after surgery.

中文翻译:

舒尼替尼和Ce6通过氧化还原反应性两性离子水凝胶的局部递送有效地防止了骨肉瘤的复发。

手术结合辅助或新辅助化疗仍是骨肉瘤的标准治疗方法。然而,肿瘤复发的高风险和化学疗法的副作用通常导致癌症患者的高死亡率。本文中,多目标受体酪氨酸激酶(RTK)抑制剂舒尼替尼(Sunitinib)和光动力疗法(PDT)药物二氢卟酚e6(Ce6)通过两性离子水凝胶局部递送至术后肿瘤部位。该水凝胶表现出优异的生物相容性和氧化还原反应性。体外研究表明,Sun / Ce6 @ Gel通过下调Bcl-2的表达并上调Bax和caspase-3的表达来诱导143B人骨肉瘤细胞凋亡。同样,体内研究表明,Sun / Ce6 @ Gel在氧化还原条件下提供了持续的药物释放,然后协同诱导肿瘤细胞凋亡以防止肿瘤复发而没有全身毒性。因此,Sun / Ce6 @ Gel的局部植入可能是预防手术后骨肉瘤复发的有前途的局部治疗方法。
更新日期:2020-08-05
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