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Ultra pH-sensitive polymeric nanovesicles co-deliver doxorubicin and navitoclax for synergetic therapy of endometrial carcinoma
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-02-25 , DOI: 10.1039/d0bm00112k Jie Ding 1, 2, 3, 4 , Xu Zhang 1, 2, 3, 4 , Chuangqi Chen 4, 5, 6, 7 , Yuqiang Huang 4, 5, 6, 7 , Xingsu Yu 4, 5, 6, 7 , Xiaomao Li 1, 2, 3, 4
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-02-25 , DOI: 10.1039/d0bm00112k Jie Ding 1, 2, 3, 4 , Xu Zhang 1, 2, 3, 4 , Chuangqi Chen 4, 5, 6, 7 , Yuqiang Huang 4, 5, 6, 7 , Xingsu Yu 4, 5, 6, 7 , Xiaomao Li 1, 2, 3, 4
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Endometrial carcinoma is a kind of epithelial malignant tumor occurring in the endometrium with high incidence (nearly 200 000 people are diagnosed every year). At present, surgery is the main strategy for the treatment of endometrial carcinoma. However, in special cases such as serous, clear cell carcinoma and postoperative recurrences, chemotherapy is still essential and indispensable. The combined chemotherapy schemes of cisplatin, paclitaxel and doxorubicin (DOX) in clinical applications are unfortunately complicated and easily cause severe side effects. In recent years, with the development of nanotechnology, the targeted delivery of multi-chemotherapeutic drugs shows great advantages in reducing side effects and improving anticancer efficacy. Here, an ultra pH-sensitive nanovesicle based on polyethylene glycol-poly(diisopropylamino)ethyl methacrylate (PEG-PDPA) was fabricated. A chemotherapeutic drug (doxorubicin) and an anti-apoptotic Bcl-2 inhibitor (navitoclax) were co-encapsulated in the hydrophilic cavity and hydrophobic membrane of the vesicle, respectively. After accumulating in the tumor tissue via the enhanced permeability and retention (EPR) effect, the nanovesicles could be efficiently diffused in tumor cells by endocytosis and then rapidly release drugs in response to the lysosomal acidic environment, leading to an enhanced tumor-killing effect based on the combination therapy between DOX and the Bcl-2 inhibitor. The drug co-delivery system and microenvironment-triggered drug release may provide an efficient strategy for endometrial carcinoma therapy.
中文翻译：
超pH敏感的聚合物纳米囊泡可共同递送阿霉素和纳维托克，用于子宫内膜癌的协同治疗
子宫内膜癌是一种发生在子宫内膜的上皮恶性肿瘤，发病率很高（每年诊断出近20万人）。目前，手术是治疗子宫内膜癌的主要策略。但是，在浆液性，透明细胞癌和术后复发等特殊情况下，化学疗法仍然是必不可少且必不可少的。不幸的是，在临床应用中，顺铂，紫杉醇和阿霉素（DOX）的联合化疗方案非常复杂，容易引起严重的副作用。近年来，随着纳米技术的发展，多种化疗药物的靶向递送在减少副作用和提高抗癌功效方面显示出巨大的优势。这里，制备了基于聚乙二醇-聚（二异丙基氨基）甲基丙烯酸乙酯（PEG-PDPA）的超pH敏感性纳米囊泡。将化学治疗药物（阿霉素）和抗凋亡Bcl-2抑制剂（navitoclax）分别包囊在囊泡的亲水腔和疏水膜中。在肿瘤组织中积累后通过增强的通透性和保留（EPR）效应，纳米囊泡可以通过内吞作用在肿瘤细胞中有效扩散，然后响应溶酶体酸性环境而迅速释放药物，从而基于DOX之间的联合疗法增强了肿瘤杀伤作用和Bcl-2抑制剂。药物共递送系统和微环境触发的药物释放可能为子宫内膜癌治疗提供有效策略。
更新日期：2020-02-25
中文翻译：
超pH敏感的聚合物纳米囊泡可共同递送阿霉素和纳维托克，用于子宫内膜癌的协同治疗
子宫内膜癌是一种发生在子宫内膜的上皮恶性肿瘤，发病率很高（每年诊断出近20万人）。目前，手术是治疗子宫内膜癌的主要策略。但是，在浆液性，透明细胞癌和术后复发等特殊情况下，化学疗法仍然是必不可少且必不可少的。不幸的是，在临床应用中，顺铂，紫杉醇和阿霉素（DOX）的联合化疗方案非常复杂，容易引起严重的副作用。近年来，随着纳米技术的发展，多种化疗药物的靶向递送在减少副作用和提高抗癌功效方面显示出巨大的优势。这里，制备了基于聚乙二醇-聚（二异丙基氨基）甲基丙烯酸乙酯（PEG-PDPA）的超pH敏感性纳米囊泡。将化学治疗药物（阿霉素）和抗凋亡Bcl-2抑制剂（navitoclax）分别包囊在囊泡的亲水腔和疏水膜中。在肿瘤组织中积累后通过增强的通透性和保留（EPR）效应，纳米囊泡可以通过内吞作用在肿瘤细胞中有效扩散，然后响应溶酶体酸性环境而迅速释放药物，从而基于DOX之间的联合疗法增强了肿瘤杀伤作用和Bcl-2抑制剂。药物共递送系统和微环境触发的药物释放可能为子宫内膜癌治疗提供有效策略。
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