Targeted delivery of cytotoxic proteins via lipid-based nanoparticles to primary Langerhans cells†

IF 5.8 3区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Nanoscale Pub Date : 2024-12-09 DOI:10.1039/D4NR03638G
Nowras Rahhal, Mareike Rentzsch, Saskia Seiser, Christian Freystätter, Adelheid Elbe-Bürger and Christoph Rademacher
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引用次数: 0

Abstract

Targeted delivery has emerged as a critical strategy in the development of novel therapeutics. The advancement of nanomedicine hinges on the safe and precise cell-specific delivery of protein-based therapeutics to the immune system. However, major challenges remain, such as developing an efficient delivery system, ensuring specificity, minimizing off-target effects, and attaining effective intracellular localization. Our strategy utilizes lipid-based nanoparticles conjugated with a glycomimetic ligand. These nanoparticles selectively bind to langerin, a C-type lectin receptor expressed on Langerhans cells in the skin. We opted for cytotoxic proteins, namely cytochrome c and saporin, as model proteins to showcase the potential of delivering intact proteins to Langerhans cells. These proteins are recognized for their ability to induce apoptosis upon entry into the cytosol. We observed specific killing of cells expressing langerin in vitro, and in primary Langerhans cells isolated from mouse and human skin ex vivo with minimal off target effects. By delivering functional proteins within lipid nanoparticles to Langerhans cells, our approach offers new potential to deliver effective therapeutics with minimal side effects.

Abstract Image

通过脂基纳米颗粒靶向递送细胞毒性蛋白至朗格汉斯细胞
靶向递送已成为开发新型治疗方法的关键策略。纳米医学的进步取决于安全、精确地将基于蛋白质的治疗药物输送到免疫系统。然而,主要的挑战仍然存在,如开发一个有效的递送系统,确保特异性,最小化脱靶效应,并获得有效的细胞内定位。我们的策略是利用基于脂质的纳米颗粒与拟糖配体缀合。这些纳米颗粒选择性地与朗格汉斯细胞中唯一表达的c型凝集素受体朗格汉斯结合。我们选择细胞毒性蛋白,即细胞色素C和皂苷作为模型蛋白,以展示将完整蛋白递送到朗格汉斯细胞的潜力。这些蛋白因其进入细胞质后诱导细胞凋亡的能力而被认可。我们在体外以及从小鼠和人皮肤分离的原代朗格汉斯细胞中观察到表达朗格兰素的细胞的特异性杀伤,并且具有最小的脱靶效应。通过将脂质纳米颗粒内的功能蛋白输送到朗格汉斯细胞,我们的方法提供了一种新的潜力,可以提供副作用最小的有效治疗方法。
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来源期刊
Nanoscale
Nanoscale CHEMISTRY, MULTIDISCIPLINARY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
12.10
自引率
3.00%
发文量
1628
审稿时长
1.6 months
期刊介绍: Nanoscale is a high-impact international journal, publishing high-quality research across nanoscience and nanotechnology. Nanoscale publishes a full mix of research articles on experimental and theoretical work, including reviews, communications, and full papers.Highly interdisciplinary, this journal appeals to scientists, researchers and professionals interested in nanoscience and nanotechnology, quantum materials and quantum technology, including the areas of physics, chemistry, biology, medicine, materials, energy/environment, information technology, detection science, healthcare and drug discovery, and electronics.
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