当前位置: X-MOL 学术Adv. Healthcare Mater. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Engineering of a Core-Shell Nanoplatform to Overcome Multidrug Resistance via ATP Deprivation.
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-09-18 , DOI: 10.1002/adhm.202000432
Genhua Liu 1 , Liucan Wang 1 , Junjie Liu 1 , Lu Lu 1 , Dong Mo 1 , Ke Li 1 , Xin Yang 1 , Rui Zeng 1 , Jixi Zhang 1 , Peng Liu 1, 2 , Kaiyong Cai 1, 2
Affiliation  

Inhibiting the function of P‐glycoprotein (P‐gp) transporter, which causes drug efflux through adenosine triphosphate (ATP)‐dependent manner, has become an effective strategy to conquer multidrug resistance (MDR) of cancer cells. However, there remains challenges for effective co‐delivery, sequential release of P‐gp modulator and chemotherapeutic agent. In this work, a novel type of core–shell nanoparticle is reported. It can independently encapsulate a high amount (about 683 µg mg−1) of chemotherapeutic agent doxorubicin (DOX) in the mesoporous polydopamine (MPDA) core and glucose oxidase (GOx) in the zeolite imidazolate frameworks‐8 (ZIF‐8) shell, namely MPDA@ZIF‐8/DOX+GOx. The fast release of GOx triggered by acid‐sensitive degradation of the ZIF‐8 shell consumes glucose to starve cancer cells for ATP deprivation and effective suppress ATP‐dependent drug efflux in advance, and then effectively facilitates the accumulation of DOX in MCF‐7/ADR cancer cells. Experiments in vitro and in vivo demonstrate that the fabricated nanosystem can dramatically improve anticancer effects for MDR through sequential release property and exhibit excellent biocompatibility. Overall, this work reveals new insights in the use of GOx for MDR treatment.

中文翻译:

通过ATP剥夺克服多药耐药性的核-壳纳米平台的工程设计。

抑制P-糖蛋白(P-gp)转运蛋白的功能通过依赖三磷酸腺苷(ATP)的方式引起药物外排,已成为征服癌细胞多药耐药性(MDR)的有效策略。但是,有效的共递送,P-gp调节剂和化学治疗剂的顺序释放仍然存在挑战。在这项工作中,报道了一种新型的核壳纳米粒子。它可以独立地封装大量(约683 µg mg -1)介孔聚多巴胺(MPDA)核心中的阿霉素(DOX)和沸石咪唑酸酯骨架8(ZIF-8)外壳中的葡萄糖氧化酶(GOx),即MPDA @ ZIF-8 / DOX + GOx。ZIF-8壳的酸敏感性降解引发的GOx的快速释放会消耗葡萄糖,使癌细胞饿死以进行ATP剥夺,并预先有效地抑制ATP依赖性药物外排,然后有效促进DOX在MCF-7 / ADR癌细胞。体外和体内实验表明,所制备的纳米系统可通过顺序释放特性显着改善MDR的抗癌作用,并具有出色的生物相容性。总的来说,这项工作揭示了使用GOx进行MDR治疗的新见解。
更新日期:2020-10-22
down
wechat
bug