使用含有两种不同氨基酸降解酶的纳米颗粒抑制癌细胞生长

IF 2.1 4区 材料科学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Shuhei Murayama, Hiromu Kurase, Kanako Tatsubori, Kyoko Takemura, Takashi Takaki, Masaru Kato
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引用次数: 0

摘要

尽管消耗氨基酸是抑制肿瘤生长的有效策略,但用于此目的的氨基酸降解酶在体内会降解,因此必须稳定并迅速引入靶细胞。本研究的目的是探索抑制癌细胞增殖的新策略,同时最大限度地减少脱靶效应。具体来说,我们专注于氨基酸剥夺方法,针对必需氨基酸精氨酸和天冬酰胺,这是癌细胞增殖和存活所必需的。在这里,我们报道了氨基酸降解酶的稳定和功能表达,使用具有网络结构的纳米颗粒,可以快速(在20分钟内)引入细胞。使用该系统,根据网孔大小,大分子(如酶)被阻挡,而小分子(如氨基酸)可以自由通过。这有助于将酶与纳米颗粒一起引入细胞,在稳定状态下降解氨基酸。这些结果表明,该系统有潜力用于氨基酸耗竭治疗以外的目的,因为它的应用使多种酶在细胞内以稳定状态发挥作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Suppression of cancer cell growth using nanoparticles containing two different amino acid-degrading enzymes

Although depleting amino acids is a useful strategy for suppressing tumor growth, the amino acid-degrading enzymes used for this purpose are degraded in vivo, and they must be stabilized and rapidly introduced into target cells. The aim of this study was to explore novel strategies for suppressing cancer cell proliferation while minimizing off-target effects. Specifically, we focused on an amino acid deprivation approach, targeting the essential amino acids arginine and asparagine, which are integral to the proliferation and survival of cancer cells. Here, we report the stabilization and functional expression of amino acid-degrading enzymes using a developed nanoparticle with a network structure, which could be rapidly (in 20 min) introduced into the cell. Using this system, depending on the mesh size, macromolecules (as enzymes) are blocked, whereas small molecules (as amino acids) can freely pass through. This facilitates the introduction of enzymes into cells, along with nanoparticles, to degrade amino acids in a stable state. These results suggest that this system has the potential to be utilized for purposes other than amino acid depletion therapy, as its application enables multiple enzymes to function within cells in a stabilized state.

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来源期刊
Journal of Nanoparticle Research
Journal of Nanoparticle Research 工程技术-材料科学:综合
CiteScore
4.40
自引率
4.00%
发文量
198
审稿时长
3.9 months
期刊介绍: The objective of the Journal of Nanoparticle Research is to disseminate knowledge of the physical, chemical and biological phenomena and processes in structures that have at least one lengthscale ranging from molecular to approximately 100 nm (or submicron in some situations), and exhibit improved and novel properties that are a direct result of their small size. Nanoparticle research is a key component of nanoscience, nanoengineering and nanotechnology. The focus of the Journal is on the specific concepts, properties, phenomena, and processes related to particles, tubes, layers, macromolecules, clusters and other finite structures of the nanoscale size range. Synthesis, assembly, transport, reactivity, and stability of such structures are considered. Development of in-situ and ex-situ instrumentation for characterization of nanoparticles and their interfaces should be based on new principles for probing properties and phenomena not well understood at the nanometer scale. Modeling and simulation may include atom-based quantum mechanics; molecular dynamics; single-particle, multi-body and continuum based models; fractals; other methods suitable for modeling particle synthesis, assembling and interaction processes. Realization and application of systems, structures and devices with novel functions obtained via precursor nanoparticles is emphasized. Approaches may include gas-, liquid-, solid-, and vacuum-based processes, size reduction, chemical- and bio-self assembly. Contributions include utilization of nanoparticle systems for enhancing a phenomenon or process and particle assembling into hierarchical structures, as well as formulation and the administration of drugs. Synergistic approaches originating from different disciplines and technologies, and interaction between the research providers and users in this field, are encouraged.
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