Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
Reproductive Center, Guangdong Women's Health Care Center, Guangzhou 511400, China.
Biomater Sci. 2020 Apr 15;8(8):2264-2273. doi: 10.1039/d0bm00112k.
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.
子宫内膜癌是一种发生于子宫内膜的上皮性恶性肿瘤，发病率较高（每年约有 20 万人被诊断）。目前，手术是治疗子宫内膜癌的主要策略。然而，在特殊情况下，如浆液性、透明细胞癌和术后复发，化疗仍然是必要的。在临床应用中，顺铂、紫杉醇和多柔比星（DOX）联合化疗方案虽然复杂，但不幸的是，容易引起严重的副作用。近年来，随着纳米技术的发展，多化疗药物的靶向递送在降低副作用和提高抗癌疗效方面显示出巨大优势。在这里，我们制备了一种基于聚乙二醇-聚（二异丙基氨基）乙基甲基丙烯酸酯（PEG-PDPA）的超 pH 敏感纳米囊泡。将化疗药物（多柔比星）和抗凋亡 Bcl-2 抑制剂（navitoclax）分别包封在囊泡的亲水腔和疏水膜中。通过增强渗透和保留（EPR）效应在肿瘤组织中积累后，纳米囊泡可以通过内吞作用被有效扩散到肿瘤细胞中，然后在溶酶体酸性环境下迅速释放药物，从而基于 DOX 和 Bcl-2 抑制剂的联合治疗产生增强的肿瘤杀伤效果。该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一种有效的策略。
