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Transmembrane TNFα-Expressed Macrophage Membrane-Coated Chitosan Nanoparticles as Cancer Therapeutics.
ACS Omega ( IF 3.7 ) Pub Date : 2020-01-13 , DOI: 10.1021/acsomega.9b03531 Srirupa Bhattacharyya 1 , Siddhartha Sankar Ghosh 1
ACS Omega ( IF 3.7 ) Pub Date : 2020-01-13 , DOI: 10.1021/acsomega.9b03531 Srirupa Bhattacharyya 1 , Siddhartha Sankar Ghosh 1
Affiliation
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Transmembrane TNFα, a crucial signaling cytokine, holds anticell proliferative potential. Successful delivery of this intact transmembrane protein to the target site is quite intriguing. Amidst numerous nanocarriers, a novel class of new generation macrophage membrane-coated nanocarriers is endowed with innate tumor homing abilities and inherent capacity of escaping body's defense machinery. In this perspective, a novel therapeutic module has been fabricated by coating a nontoxic, biodegradable chitosan nanoparticle core with engineered macrophage membrane-tethered TNFα. Herein, the expression of membrane-bound TNFα was induced by challenging phorbol 12-myristate 13-acetate-differentiated THP-1 cells with bacterial lipopolysaccharide. Subsequently, the as-synthesized chitosan nanoparticle core was coated with a TNFα-expressed macrophage membrane through an extrusion process. While transmission electron microscopy imaging, sodium dodecyl sulphate polyacrylamide gel electrophoresis, and western blotting results demonstrated successful coating of the chitosan nanoparticles with the TNFα-induced membrane, the cell viability assays on several cancer cells such as-HeLa, MDA-MB-231, and MCF-7 revealed significant innate anticell proliferative potential of these membrane-coated nanoparticles. Additionally, evaluation of expression of several interleukins after treatment demonstrated excellent biocompatibility of the membrane-coated nanoparticles. The fabricated nanoparticles also demonstrated a dose-dependent cell death in tumor spheroids, which was further corroborated with calcein AM/propidium iodide dual staining results. Translation of the therapeutic efficacy of the synthesized nanoparticles from monolayers to tumor spheroids augments its potential in cancer therapy.
中文翻译：
跨膜 TNFα 表达的巨噬细胞膜包被的壳聚糖纳米颗粒作为癌症治疗药物。
跨膜 TNFα 是一种重要的信号细胞因子，具有抗细胞增殖潜力。将这种完整的跨膜蛋白成功递送至靶位点是非常有趣的。在众多的纳米载体中，一类新型的新一代巨噬细胞膜包被的纳米载体被赋予了先天的肿瘤归巢能力和逃避人体防御机制的固有能力。从这个角度来看，通过用工程巨噬细胞膜束缚的 TNFα 涂覆无毒、可生物降解的壳聚糖纳米颗粒核心，制备了一种新型治疗模块。在此，通过用细菌脂多糖攻击佛波醇 12-肉豆蔻酸酯 13-乙酸酯分化的 THP-1 细胞来诱导膜结合 TNFα 的表达。随后，通过挤出过程将合成的壳聚糖纳米颗粒核心涂上表达 TNFα 的巨噬细胞膜。透射电子显微镜成像、十二烷基硫酸钠聚丙烯酰胺凝胶电泳和蛋白质印迹结果表明，用 TNFα 诱导的膜成功涂覆了壳聚糖纳米颗粒，对几种癌细胞（如 HeLa、MDA-MB-231、 MCF-7 揭示了这些膜包被的纳米粒子显着的先天抗细胞增殖潜力。此外，对治疗后几种白细胞介素表达的评估表明，膜包被的纳米颗粒具有优异的生物相容性。所制造的纳米颗粒还表现出肿瘤球体中剂量依赖性细胞死亡，钙黄绿素 AM/碘化丙啶双重染色结果进一步证实了这一点。将合成纳米颗粒的治疗功效从单层转化为肿瘤球体增强了其在癌症治疗中的潜力。
更新日期：2020-01-29
中文翻译：
跨膜 TNFα 表达的巨噬细胞膜包被的壳聚糖纳米颗粒作为癌症治疗药物。
跨膜 TNFα 是一种重要的信号细胞因子，具有抗细胞增殖潜力。将这种完整的跨膜蛋白成功递送至靶位点是非常有趣的。在众多的纳米载体中，一类新型的新一代巨噬细胞膜包被的纳米载体被赋予了先天的肿瘤归巢能力和逃避人体防御机制的固有能力。从这个角度来看，通过用工程巨噬细胞膜束缚的 TNFα 涂覆无毒、可生物降解的壳聚糖纳米颗粒核心，制备了一种新型治疗模块。在此，通过用细菌脂多糖攻击佛波醇 12-肉豆蔻酸酯 13-乙酸酯分化的 THP-1 细胞来诱导膜结合 TNFα 的表达。随后，通过挤出过程将合成的壳聚糖纳米颗粒核心涂上表达 TNFα 的巨噬细胞膜。透射电子显微镜成像、十二烷基硫酸钠聚丙烯酰胺凝胶电泳和蛋白质印迹结果表明，用 TNFα 诱导的膜成功涂覆了壳聚糖纳米颗粒，对几种癌细胞（如 HeLa、MDA-MB-231、 MCF-7 揭示了这些膜包被的纳米粒子显着的先天抗细胞增殖潜力。此外，对治疗后几种白细胞介素表达的评估表明，膜包被的纳米颗粒具有优异的生物相容性。所制造的纳米颗粒还表现出肿瘤球体中剂量依赖性细胞死亡，钙黄绿素 AM/碘化丙啶双重染色结果进一步证实了这一点。将合成纳米颗粒的治疗功效从单层转化为肿瘤球体增强了其在癌症治疗中的潜力。
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