六方囊泡和立方囊泡的 pH 响应性用于联合递送油和阿霉素。
pH Responsiveness of Hexosomes and Cubosomes for Combined Delivery of Oil and Doxorubicin.
机构信息
Shanghai Key Laboratory of Functional Materials Chemistry, State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry, School of Chemistry and Molecular Engineering , East China University of Science and Technology , Shanghai 200237 , P. R. China.
Institut Galien Paris-Sud , CNRS UMR 8612, Univ. Paris-Sud, Université Paris-Saclay, LabEx LERMIT , F-92296 Châtenay-Malabry cedex, France.
出版信息
Langmuir. 2019 Nov 12;35(45):14532-14542. doi: 10.1021/acs.langmuir.9b02257. Epub 2019 Nov 4.
We report pH-responsive liquid crystalline lipid nanoparticles, which are dual-loaded by oil (BJO) and doxorubicin hydrochloride (DOX) and display a pH-induced inverted hexagonal (pH = 7.4) to cubic (pH = 6.8) to emulsified microemulsion (pH = 5.3) phase transition with a therapeutic application in cancer inhibition. BJO is a traditional herbal medicine that strongly inhibits the proliferation and metastasis of various cancers. Doxorubicin is an antitumor drug, which prevents DNA replication and hampers protein synthesis through intercalation between the base pairs of the DNA helices. Its dose-dependent cardiotoxicity imposes the need for safe delivery carriers. Here, pH-induced changes in the structural and interfacial properties of designed multicomponent drug delivery (monoolein-oleic acid-BJO-DOX) systems are determined by synchrotron small-angle X-ray scattering and the Langmuir film balance technique. The nanocarrier assemblies display good physical stability in the studied pH range and adequate particle sizes and ζ-potentials. Their interaction with model lipid membrane interfaces is enhanced under acidic pH conditions, which mimic the microenvironment around tumor cells. In vitro cytotoxicity and apoptosis studies with BJO-DOX dual-loaded pH-switchable liquid crystalline nanoparticles are performed on the human breast cancer Michigan Cancer Foundation-7 (MCF-7) cell line and MCF-7 cells with doxorubicin resistance (MCF-7/DOX), respectively. The obtained pH-sensitive nanomedicines exhibit enhanced antitumor efficacy. The performed preliminary studies suggest a potential reversal of the resistance of the MCF-7/DOX cells to DOX. These results highlight the necessity for further understanding the link between the established pH-dependent drug release profiles of the nanocarriers and the role of their pH-switchable inverted hexagonal, bicontinuous cubic, and emulsified microemulsion inner organizations for therapeutic outcomes.
我们报告了 pH 响应性液晶脂纳米粒，其双重负载油（BJO）和盐酸多柔比星（DOX），并显示出 pH 诱导的从六方（pH = 7.4）到立方（pH = 6.8）再到乳化微乳液（pH = 5.3）的相转变，具有抑制癌症的治疗应用。BJO 是一种传统的草药，强烈抑制各种癌症的增殖和转移。多柔比星是一种抗肿瘤药物，通过插入 DNA 螺旋的碱基对来阻止 DNA 复制并阻碍蛋白质合成。其剂量依赖性的心脏毒性需要安全的递送载体。在这里，通过同步加速器小角 X 射线散射和 Langmuir 膜天平技术确定了设计的多组分药物递送（单油酸甘油酯-油酸-BJO-DOX）系统的结构和界面特性随 pH 的变化。纳米载体组装在研究的 pH 范围内显示出良好的物理稳定性，具有适当的粒径和 ζ-电位。在酸性 pH 条件下，它们与模型脂质膜界面的相互作用增强，模拟了肿瘤细胞周围的微环境。在体外，用 BJO-DOX 双重负载 pH 开关液晶纳米粒对人乳腺癌 Michigan Cancer Foundation-7（MCF-7）细胞系和具有多柔比星耐药性的 MCF-7/DOX 细胞（MCF-7/DOX）进行了细胞毒性和凋亡研究。所得到的 pH 敏感的纳米药物表现出增强的抗肿瘤功效。进行的初步研究表明，有可能逆转 MCF-7/DOX 细胞对 DOX 的耐药性。这些结果突出表明，需要进一步了解纳米载体建立的 pH 依赖性药物释放谱与它们的 pH 可切换的反向六方、双连续立方和乳化微乳液内部组织在治疗效果中的作用之间的联系。
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