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Zwitterionic Polymer Coating of Sulfur Dioxide-Releasing Nanosystem Augments Tumor Accumulation and Treatment Efficacy.
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-01-28 , DOI: 10.1002/adhm.201901582
Xianxian Yao 1 , Shuangping Ma 2 , Shaojun Peng 1 , Gaoxin Zhou 3 , Ruihong Xie 1 , Qin Jiang 1 , Shengdi Guo 1 , Qianjun He 3 , Wuli Yang 1
Affiliation  

Multiple drug resistance (MDR) exhibited by cancer cells and low intratumor accumulation of chemotherapeutics are the main obstacles in cancer chemotherapy. Herein, the preparation of a redox-responsive sulfur dioxide (SO2 )-releasing nanosystem, with high SO2 -loading capacity, aimed at improving the treatment efficacy of cancers exhibiting MDR is described. The multifunctional nanomedicine (MON-DN@PCBMA-DOX) is designed and constructed by coating mesoporous organosilica nanoparticles with a zwitterionic polymer, poly(carboxybetaine methacrylate) (PCBMA), which can concurrently load SO2 prodrug molecules (DN, 2,4-dinitrobenzenesulfonylchloride) and chemotherapeutics (DOX, doxorubicin). The generated SO2 molecules can sensitize cells to chemotherapy and overcome the MDR by downregulating the expression of P-glycoprotein. Furthermore, the PCBMA coating prolongs the blood circulation time of the inner core, leading to an increased intratumor accumulation of the nanomedicine. Owing to the prolonged blood circulation, enhanced tumor accumulation, and SO2 sensitization of cells to chemotherapy, the nanomedicine exhibits excellent tumor suppression with a tumor inhibition rate of 94.8%, and might provide a new platform for cancer therapy.

中文翻译:

释放二氧化硫的两性离子聚合物涂层增强了肿瘤的积累和治疗功效。

癌细胞表现出的多重耐药性和化疗药物在肿瘤中的低积累是癌症化疗的主要障碍。在此,描述了具有高SO 2负载能力的旨在释放氧化还原响应性二氧化硫(SO 2)的纳米系统的制备,其旨在改善表现出MDR的癌症的治疗功效。多功能纳米药物(MON-DN @ PCBMA-DOX)是通过用两性离子聚合物聚甲基丙烯酸甜菜碱酯(PCBMA)涂覆中孔有机二氧化硅纳米颗粒而设计和构造的,该两性离子聚合物可以同时加载SO2前药分子(DN,2,4-二硝基苯磺酰氯) )和化学治疗剂(DOX,阿霉素)。产生的SO2分子可使细胞对化学疗法敏感,并通过下调P-糖蛋白的表达来克服MDR。此外,PCBMA涂层延长了内核的血液循环时间,导致纳米药物在肿瘤内的积累增加。由于血液循环的延长,肿瘤积累的增加以及细胞对化学疗法的SO2敏感性,纳米药物表现出优异的肿瘤抑制作用,其肿瘤抑制率为94.8%,并可能为癌症治疗提供新的平台。
更新日期:2020-03-04
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