Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, P. R. China.
Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai 200444, P. R. China.
ACS Appl Mater Interfaces. 2022 May 18;14(19):21954-21965. doi: 10.1021/acsami.2c02552. Epub 2022 May 4.
Ovarian cancer is a common gynecologic malignancy with a high fatality rate. Intraperitoneal chemotherapy has been proved as an efficient clinical treatment for disseminated ovarian cancer. However, there are limitations for conventional small molecule drugs to achieve an ideal therapeutic effect. Herein, a synergistic treatment for intraperitoneally disseminated ovarian cancer was achieved by Arg-Gly-Asp (RGD)-modified amorphous calcium phosphate loading with doxorubicin (designated as RGD-CaPO/DOX). The engineered calcium-involved nanomedicine augmented the therapeutic effect of DOX by aggravating endoplasmic reticulum stress, calcium overload, and mitochondrial dysfunction, ultimately triggering mitochondrial apoptosis in the SKOV3 (human ovarian cancer) cell line. In an intraperitoneally disseminated tumor model, RGD modification and the weak negative surface potential of the NPs were beneficial for intraperitoneal retention and tumor targeting. Moreover, intraperitoneal injection of RGD-CaPO/DOX NPs resulted in a favorable antitumor effect. The mean survival time of SKOV3-bearing mice was significantly extended from 29 to 59 days with negligible toxicity. Therefore, this study has been designed to provide an effective chemotherapeutic-augmented treatment for intraperitoneally disseminated ovarian cancer.
卵巢癌是一种常见的妇科恶性肿瘤，死亡率很高。腹腔内化疗已被证明是治疗播散性卵巢癌的一种有效临床治疗方法。然而，传统的小分子药物在实现理想的治疗效果方面存在局限性。在此，通过 Arg-Gly-Asp（RGD）修饰的载阿霉素无定形磷酸钙（命名为 RGD-CaPO/DOX）实现了腹腔内播散性卵巢癌的协同治疗。该工程化的钙参与纳米药物通过加重内质网应激、钙超载和线粒体功能障碍来增强 DOX 的治疗效果，最终在 SKOV3（人卵巢癌细胞系）中触发线粒体凋亡。在腹腔内播散性肿瘤模型中，RGD 修饰和 NPs 的弱负表面电势有利于腹腔内保留和肿瘤靶向。此外，腹腔内注射 RGD-CaPO/DOX NPs 可产生良好的抗肿瘤作用。荷 SKOV3 小鼠的平均存活时间从 29 天显著延长至 59 天，且毒性可忽略不计。因此，本研究旨在为腹腔内播散性卵巢癌提供一种有效的化疗增强治疗方法。
