Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Int J Nanomedicine. 2020 Oct 29;15:8427-8436. doi: 10.2147/IJN.S272319. eCollection 2020.
Epithelial ovarian cancer (EOC) is a fatal gynecologic malignancy that is usually treated with chemotherapy after surgery. However, patients who receive chemotherapy experience severe side effects because of the inherent toxicity and high dose of chemotherapeutics. To overcome these issues, we suggest a combination therapeutic strategy using liposomes encapsulating linalool nanoemulsions (LN-NEs) and doxorubicin (DOX), a chemotherapeutic drug, to increase their synergistic antitumor efficacy and reduce the incidence of side effects from chemotherapeutics for EOC.
The physical properties of LN-NE-DOX-liposomes were characterized by light scattering with a particle size analyzer. Cell viability was determined by MTT assay. Therapeutic efficacy was evaluated in a mouse HeyA8 EOC tumor model of ovarian carcinoma. Additionally, biochemical toxicity was analyzed for levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and blood urea nitrogen (BUN) using BALB/c nude mice.
The size of the liposomes encapsulating LN-NEs and DOX (LN-NE-DOX-liposomes) was 267.0 ± 4.6 nm, with a loading efficiency of 55.1 ± 3.1% and 27.2 ± 0.9% for linalool and DOX, respectively. Cell viability after treatment with LN-NE-DOX-liposomes was significantly decreased compared to that of cells treated with DOX liposomes, and apoptosis was significantly increased. Additionally, LN-NE-DOX-liposomes significantly inhibited HeyA8 EOC tumor growth compared to that of the control ( < 0.01) and DOX-liposome-treated groups ( < 0.05), while decreasing cell proliferation (Ki67) and microvessel density (CD31), and promoting apoptosis (caspase-3) compared to the control ( < 0.05). Moreover, the liposomal formulations induced no significant differences in biochemical toxicity (AST, ALT, and BUN) compared to healthy control mice, indicating that the liposomal formulations showed no overt toxicity in mice.
This study demonstrates that the production of LN-NE-DOX-liposomes is a pivotal approach for EOC treatment, suggesting a novel combination therapeutic strategy.
上皮性卵巢癌（EOC）是一种致命的妇科恶性肿瘤，通常在手术后进行化疗。然而，接受化疗的患者由于化疗药物固有的毒性和高剂量，会经历严重的副作用。为了克服这些问题，我们建议采用脂质体包封的芳樟醇纳米乳液（LN-NE）和阿霉素（DOX）的联合治疗策略，以提高其协同抗肿瘤疗效并降低 EOC 化疗药物的副作用发生率。
采用光散射法通过粒径分析仪对 LN-NE-DOX-脂质体的物理性质进行了表征。通过 MTT 测定法测定细胞活力。在卵巢癌 HeyA8 EOC 肿瘤模型中评估了治疗效果。此外，使用 BALB/c 裸鼠分析了天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）和血尿素氮（BUN）的生化毒性。
包封 LN-NE 和 DOX 的脂质体（LN-NE-DOX-脂质体）的粒径为 267.0 ± 4.6nm，包封效率分别为 55.1 ± 3.1%和 27.2 ± 0.9%，对于芳樟醇和 DOX。与 DOX 脂质体处理的细胞相比，用 LN-NE-DOX-脂质体处理后的细胞活力明显降低，且细胞凋亡明显增加。此外，与对照组（<0.01）和 DOX-脂质体处理组（<0.05）相比，LN-NE-DOX-脂质体显著抑制 HeyA8 EOC 肿瘤生长，同时降低细胞增殖（Ki67）和微血管密度（CD31），并促进细胞凋亡（caspase-3）与对照组相比（<0.05）。此外，与健康对照组相比，脂质体制剂在生化毒性（AST、ALT 和 BUN）方面没有引起显著差异，表明脂质体制剂在小鼠中没有明显的毒性。
本研究表明，LN-NE-DOX-脂质体的制备是治疗 EOC 的关键方法，提示了一种新的联合治疗策略。
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