Chen Xue, Wan Haopeng, Lu Lijuan, Li Ran, Sun Bo, Ren Juan
Department of Traditional Chinese Medicine, Nanxiang Branch of Ruijin Hospital, Shanghai 201802, China.
Department of Gynecology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215000, China.
IET Nanobiotechnol. 2024 Nov 29;2024:7136323. doi: 10.1049/nbt2/7136323. eCollection 2024.
As a naturally derived inhibitor of autophagy, Kushenol E (KE) is a biprenylated flavonoid and is isolated from , which has been used for the treatment of cancer, hepatitis, and skin diseases. However, KE, as a poorly soluble drug, exhibited strong autophagy regulating activity in in vitro cancer cell lines, but no related studies have reported its antiovarian cancer property. Therefore, it is very beneficial to enhance the antineoplastic properties of KE by establishing an ovarian tumor-targeting nanoparticle system modified with tumor-homing c(RGDfK) peptides. In the current study, poly(lactic-co-glycolic acid)-poly(ethylene glycol)-modified with cyclic RGDfK peptide (PLGA-PEG-c(RGDfK))-KE micelles (PPCKM) were prepared to overcome the poor water solubility of KE to meet the requirement of tumor-active targeting. The effect of PPCKM on ovarian cancer was evaluated on SKOV-3 cells and xenograft models in BALB/c nude mice. The PPCKM showed a higher drug cumulative release ratio (82.16 ± 7.69% vs. 34.96 ± 3.05%, at 1.5 h) with good morphology, particle size (93.41 ± 2.84 nm), and entrapment efficiency (89.7% ± 1.3%). The cell viability, migration, and apoptosis analysis of SKOV-3 cells demonstrated that PPCKM retained potent antitumor effects and promoted apoptosis at early and advanced stages with concentration-dependent. Based on the establishment of xenograft models in BALB/c nude mice, we discovered that PPCKM reduced tumor volume and weight, inhibited proliferating cell nuclear antigen (PCNA) and Ki67 expression, as well as promoted apoptosis by targeting the tumor site. The findings in this study suggest that PPCKM may serve as an effective therapeutic option for ovarian cancer.
苦参醇E（KE）作为一种天然的自噬抑制剂，是一种双异戊烯基黄酮类化合物，从[具体来源未提及]中分离得到，已被用于治疗癌症、肝炎和皮肤病。然而，KE作为一种难溶性药物，在体外癌细胞系中表现出强大的自噬调节活性，但尚无相关研究报道其抗卵巢癌特性。因此，通过建立用肿瘤归巢c(RGDfK)肽修饰的卵巢肿瘤靶向纳米颗粒系统来增强KE的抗肿瘤特性是非常有益的。在本研究中，制备了用环状RGDfK肽修饰的聚乳酸-乙醇酸共聚物-聚乙二醇（PLGA-PEG-c(RGDfK)）-KE胶束（PPCKM），以克服KE的水溶性差问题，满足肿瘤活性靶向的要求。在SKOV-3细胞和BALB/c裸鼠异种移植模型上评估了PPCKM对卵巢癌的作用。PPCKM显示出更高的药物累积释放率（1.5小时时为82.16±7.69%，而[未修饰组数据]为34.96±3.05%），具有良好的形态、粒径（93.41±2.84nm）和包封率（89.7%±1.3%）。SKOV-3细胞的细胞活力、迁移和凋亡分析表明，PPCKM保留了强大的抗肿瘤作用，并在早期和晚期以浓度依赖性方式促进凋亡。基于在BALB/c裸鼠中建立的异种移植模型，我们发现PPCKM通过靶向肿瘤部位减少了肿瘤体积和重量，抑制了增殖细胞核抗原（PCNA）和Ki67的表达，并促进了凋亡。本研究结果表明，PPCKM可能是卵巢癌的一种有效治疗选择。
