使用脂质包覆碳酸钙纳米颗粒将 EV 肽靶向递送至肿瘤细胞质。
Targeted delivery of EV peptide to tumor cell cytoplasm using lipid coated calcium carbonate nanoparticles.
机构信息
Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
出版信息
Cancer Lett. 2013 Jul 1;334(2):311-8. doi: 10.1016/j.canlet.2012.07.011. Epub 2012 Jul 14.
Abstract
Intracellular-acting peptide drugs are effective for inhibiting cytoplasmic protein targets, yet face challenges with penetrating the cancer cell membrane. We have developed a lipid nanoparticle formulation that utilizes a pH-sensitive calcium carbonate complexation mechanism to enable the targeted delivery of the intracellular-acting therapeutic peptide EEEEpYFELV (EV) into lung cancer cells. Lipid-calcium-carbonate (LCC) nanoparticles were conjugated with anisamide, a targeting ligand for the sigma receptor which is expressed on lung cancer cells. LCC EV nanoparticle treatment provoked severe apoptotic effects in H460 non-small cell lung cancer cells in vitro. LCC NPs also mediated the specific delivery of Alexa-488-EV peptide to tumor tissue in vivo, provoking a high tumor growth retardation effect with minimal uptake by external organs and no toxic effects.
摘要
细胞内作用的肽类药物对于抑制细胞质蛋白靶标非常有效，但面临着穿透癌细胞膜的挑战。我们开发了一种脂质纳米颗粒制剂，利用 pH 敏感的碳酸钙复合机制，使细胞内作用的治疗性肽 EEEEpYFELV（EV）能够靶向递送至肺癌细胞。脂质-碳酸钙（LCC）纳米颗粒与茴香酰胺缀合，茴香酰胺是一种针对肺癌细胞上表达的 sigma 受体的靶向配体。LCC-EV 纳米颗粒处理在体外强烈诱导 H460 非小细胞肺癌细胞发生凋亡效应。LCC NPs 还介导了 Alexa-488-EV 肽在体内肿瘤组织的特异性递送，引起高肿瘤生长抑制作用，外部器官摄取最小，无毒性作用。
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