Yao Xianxian, Ma Shuangping, Peng Shaojun, Zhou Gaoxin, Xie Ruihong, Jiang Qin, Guo Shengdi, He Qianjun, Yang Wuli
State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai, 200433, China.
School of Life Sciences, Fudan University, Shanghai, 200433, China.
Adv Healthc Mater. 2020 Mar;9(5):e1901582. doi: 10.1002/adhm.201901582. Epub 2020 Jan 28.
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 (SO )-releasing nanosystem, with high SO -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 SO prodrug molecules (DN, 2,4-dinitrobenzenesulfonylchloride) and chemotherapeutics (DOX, doxorubicin). The generated SO 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 SO 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.
癌细胞表现出的多药耐药性（MDR）以及化疗药物在肿瘤内的低蓄积是癌症化疗的主要障碍。在此，描述了一种具有高二氧化硫（SO₂）负载能力的氧化还原响应性二氧化硫释放纳米系统的制备，旨在提高对表现出MDR的癌症的治疗效果。多功能纳米药物（MON-DN@PCBMA-DOX）是通过用两性离子聚合物聚（甲基丙烯酸羧酸甜菜碱）（PCBMA）包覆介孔有机硅纳米颗粒而设计和构建的，它可以同时负载SO₂前药分子（DN，2,4-二硝基苯磺酰氯）和化疗药物（DOX，阿霉素）。产生的SO₂分子可使细胞对化疗敏感，并通过下调P-糖蛋白的表达克服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蓄积增加。由于血液循环时间延长、肿瘤蓄积增强以及细胞对化疗的SO₂致敏作用，该纳米药物表现出优异的肿瘤抑制效果，肿瘤抑制率为94.8%，可能为癌症治疗提供一个新的平台。
