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Cyclic RGD-Peptide-Functionalized Polylipopeptide Micelles for Enhanced Loading and Targeted Delivery of Monomethyl Auristatin E
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-09-27 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00498 Min Qiu 1 , Xiuxiu Wang 1 , Huanli Sun 1 , Jian Zhang 1 , Chao Deng 1 , Zhiyuan Zhong 1
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-09-27 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00498 Min Qiu 1 , Xiuxiu Wang 1 , Huanli Sun 1 , Jian Zhang 1 , Chao Deng 1 , Zhiyuan Zhong 1
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Monomethyl auristatin E (MMAE) is an extremely potent peptide drug that is currently used in the form of antibody drug conjugates (ADCs) for treating different cancers. ADCs are, however, associated with low drug conjugation, immunogenicity, small scale production, and high costs. Here, cRGD-functionalized polylipopeptide micelles (cRGD-Lipep-Ms) were explored for enhanced loading and targeted delivery of MMAE to HCT-116 colorectal tumor xenografts. Interestingly, cRGD-Lipep-Ms achieved an MMAE loading content of 5.5 wt %, which was 55-fold higher than that of poly(ethylene glycol)-b-poly(d,l-lactide) micelles. MMAE-loaded cRGD-Lipep-Ms (MMAE-cRGD-Lipep-Ms) showed a small hydrodynamic size of 59 nm, minimal drug leakage in 10% FBS, and efficient uptake and superb antiproliferative activity in αvβ5-overexpressing HCT-116 tumor cells. Remarkably, MMAE-cRGD-Lipep-Ms displayed over 10-fold better toleration than free MMAE in mice and completely suppressed growth of HCT-116 colorectal tumor xenografts. These polylipopeptide micelles have appeared to be an attractive alternative to ADCs for targeted delivery of potent peptide drugs.
中文翻译：
环状RGD-肽功能化多脂肽胶束，用于增强单甲基Aristinatin E的负载和靶向递送
单甲基耳他汀E（MMAE）是一种非常有效的肽类药物，目前以抗体药物偶联物（ADC）的形式用于治疗不同的癌症。然而，ADC与药物结合低，免疫原性，小规模生产和高成本有关。在这里，研究了cRGD功能化的多肽肽微团（cRGD-Lipep-Ms）的增强负载和将MMAE靶向递送至HCT-116结直肠肿瘤异种移植物。有趣的是，cRGD-Lipep-Ms的MMAE负载量为5.5 wt％，比聚（乙二醇）-b - poly （d，l-丙交酯）胶束。MMAE加载的cRGD-Lipep-MS（MMAE-的cRGD-Lipep-MS）表明在α为59纳米的小流体动力学尺寸，在10％FBS的最小药物渗漏，和有效摄取和高超的抗增殖活性v β 5 -overexpressing HCT- 116个肿瘤细胞。值得注意的是，在小鼠中，MMAE-cRGD-Lipep-Ms的耐受性比游离MMAE高10倍以上，并且完全抑制了HCT-116结直肠肿瘤异种移植物的生长。这些聚脂肽胶束似乎是靶向肽有效靶向药物的ADC的有吸引力的替代品。
更新日期：2018-09-27
中文翻译：
环状RGD-肽功能化多脂肽胶束，用于增强单甲基Aristinatin E的负载和靶向递送
单甲基耳他汀E（MMAE）是一种非常有效的肽类药物，目前以抗体药物偶联物（ADC）的形式用于治疗不同的癌症。然而，ADC与药物结合低，免疫原性，小规模生产和高成本有关。在这里，研究了cRGD功能化的多肽肽微团（cRGD-Lipep-Ms）的增强负载和将MMAE靶向递送至HCT-116结直肠肿瘤异种移植物。有趣的是，cRGD-Lipep-Ms的MMAE负载量为5.5 wt％，比聚（乙二醇）-b - poly （d，l-丙交酯）胶束。MMAE加载的cRGD-Lipep-MS（MMAE-的cRGD-Lipep-MS）表明在α为59纳米的小流体动力学尺寸，在10％FBS的最小药物渗漏，和有效摄取和高超的抗增殖活性v β 5 -overexpressing HCT- 116个肿瘤细胞。值得注意的是，在小鼠中，MMAE-cRGD-Lipep-Ms的耐受性比游离MMAE高10倍以上，并且完全抑制了HCT-116结直肠肿瘤异种移植物的生长。这些聚脂肽胶束似乎是靶向肽有效靶向药物的ADC的有吸引力的替代品。
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