Background: Phytosterols significantly reduce the risk of cancer by directly inhibiting tumor growth, inducing apoptosis, and inhibiting tumor metastasis. Stigmasterol (STS), a phytosterol, exhibits anticancer effects against various cancers, including breast cancer. Chemotherapeutics, including doxorubicin (DOX), might act synergistically with phytosterol against the proliferation and metastasis of breast cancer. Although such compounds can show potential anticancer activity, their combined effect with suitable formulation has not investigated yet.Methods: Hyaluronic acid (HA)-modified PEGylated DOX-STS loaded phyto-liposome was fabricated via a thin-film hydration method. The prepared phyto-liposome was optimized with regards to its physicochemical and other properties. Further, in vitro and in vivo study was carried out in breast cancer cells expressing a different level of CD44 receptors.Results: The particle size of prepared HA-DOX-STS-lipo was 173.9 ± 2.4 nm, and showed pH-depended DOX release, favoring the effective tumor targetability. The in vitro anticancer activity of HA-DOX-STS-lipo was significantly enhanced in MDA-MB-231, CD44-overexpressing cells relative to MCF-7 cells demonstrating HA-mediated targeting effect. HA-DOX-STS-lipo accumulated more and increased antitumor efficacy in the MDA-MB-231 xenograft tumor model expressing high levels of CD44, suggesting the potential of carrier system toward CD44-overexpressing tumors.

中文翻译：

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植物甾醇负载的CD44受体靶向的聚乙二醇化纳米杂化植物脂质体，用于协同化疗。

背景：植物甾醇通过直接抑制肿瘤生长，诱导细胞凋亡和抑制肿瘤转移，显着降低癌症风险。植物甾醇Stigmasterol（STS）对多种癌症（包括乳腺癌）表现出抗癌作用。包括阿霉素（DOX）在内的化学治疗药物可能与植物甾醇协同作用，对抗乳腺癌的增殖和转移。尽管这类化合物可以显示出潜在的抗癌活性，但尚未对其与合适制剂的组合作用进行研究。方法：通过薄膜水化法制备透明质酸（HA）修饰的聚乙二醇化DOX-STS负载植物脂质体。关于所制备的植物脂质体的物理化学和其他性质进行了优化。进一步，结果：制备的HA-DOX-STS-lipo的粒径为173.9±2.4 nm，并表现出pH依赖性的DOX释放，有利于体外研究体内和体外表达CD44受体的乳腺癌细胞。有效的肿瘤靶向性。相对于MCF-7细胞，HA-DOX-STS-lipo的体外抗癌活性在MDA-MB-231，CD44过表达的细胞中得到了显着增强，这证明了HA介导的靶向作用。在表达高水平CD44的MDA-MB-231异种移植肿瘤模型中，HA-DOX-STS-lipo积累了更多的抗肿瘤药，并提高了其抗肿瘤功效，这表明载体系统有可能针对CD44过表达的肿瘤。支持有效的肿瘤靶向性。相对于证明HA介导的靶向作用的MCF-7细胞，MDA-MB-231，CD44过表达的细胞中HA-DOX-STS-lipo的体外抗癌活性显着增强。在表达高水平CD44的MDA-MB-231异种移植肿瘤模型中，HA-DOX-STS-lipo积累了更多的抗肿瘤药，并提高了其抗肿瘤功效，这表明载体系统有可能针对CD44过表达的肿瘤。支持有效的肿瘤靶向性。相对于证明HA介导的靶向作用的MCF-7细胞，MDA-MB-231，CD44过表达的细胞中HA-DOX-STS-lipo的体外抗癌活性显着增强。在表达高水平CD44的MDA-MB-231异种移植肿瘤模型中，HA-DOX-STS-lipo积累了更多的抗肿瘤药，并提高了其抗肿瘤功效，这表明载体系统有可能针对CD44过表达的肿瘤。