Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Cancer Lett. 2013 Jul 1;334(2):311-8. doi: 10.1016/j.canlet.2012.07.011. Epub 2012 Jul 14.
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.
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。
