刺激反应性纳米脂质体增强新型肽Dermaseptin-PP的抗肿瘤作用

IF 3.8 4区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS
Changhai Wang, Ziyi Dong, Qing Zhang, Mingxue Guo, Wenjun Hu, Shuang Dong, Tangthianchaichana Jakkree, Yang Lu, Shouying Du
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引用次数: 0

摘要

目的Dermaseptin-PP是一种新发现的抗肿瘤肽,具有独特的抗肿瘤机制和显著的抗肿瘤作用。然而,这种α-螺旋抗癌肽在高剂量使用时存在溶血风险,这限制了它的进一步应用。本研究旨在利用纳米技术制备一种ph响应性脂质体,der - loading - phsl,以避免Dermaseptin-PP的溶血风险,并增加其在肿瘤部位的积累,从而提高疗效和降低毒性。方法采用制备法对低负荷phsl进行表征。采用体外溶血实验和细胞毒性实验考察其溶血和肿瘤抑制作用。用流式细胞术观察不同pH条件下的细胞摄取情况,并评价pH对肿瘤细胞选择性的影响。为评价低负荷phsl的体内靶向性和抗肿瘤作用,采用裸鼠肿瘤模型进行体内分布实验和药效学实验。结果该脂质体制备方法简单,具有良好的纳米颗粒特性。将Dermaseptin-PP作为脂质体制备后,溶血作用明显降低,对肿瘤细胞的抑制作用明显增强。与普通脂质体相比,这种变化在低负载- phsl中更为显著。在模拟的酸性肿瘤微环境中,ph敏感脂质体的摄取更高,并且摄取表现出特定的酸依赖性。体内实验表明,der - loading - phsl具有明显的肿瘤靶向作用,可以显著增强Dermaseptin-PP的抗肿瘤作用。结论本研究设计的低负荷phsl是一种制备方法快速、简单、有效的脂质体,可通过增加肿瘤积累和细胞摄入量,显著降低Dermaseptin-PP的溶血毒性,增强其抗肿瘤作用。为应用Dermaseptin-PP等α-螺旋结构抗癌肽提供了新的思路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Stimulus-responsive nano lipidosome for enhancing the anti-tumour effect of a novel peptide Dermaseptin-PP

Stimulus-responsive nano lipidosome for enhancing the anti-tumour effect of a novel peptide Dermaseptin-PP

Objective

Dermaseptin-PP is a newly discovered anticancer peptide with a unique antitumour mechanism and remarkable effect. However, this α-helix anticancer peptide risks haemolysis when used at high doses, which limits its further application. This study aims to prepare a pH-responsive liposome, Der-loaded-pHSL, using nanotechnology to avoid the haemolysis risk of Dermaseptin-PP and increase its accumulation in tumour sites to enhance efficacy and reduce toxicity.

Methods

The characterisation of Der-loaded-pHSL was carried out employing preparation. The effect of haemolysis and tumour inhibition were investigated by in vitro haemolysis assay and cytotoxicity assay. The cell uptake under different pH conditions was investigated by flow cytometry, and the effect of pH on tumour cell selectivity was evaluated. In order to evaluate the in vivo targeting and antitumour effect of Der-loaded-pHSL, the in vivo distribution experiment and the pharmacodynamic experiment were performed using the nude mouse tumour model.

Results

The preparation method of the Der-loaded-pHSL is simple, and the liposome has good nanoparticle characteristics. When Dermaseptin-PP was prepared as liposome, haemolysis was significantly decreased, and tumour cell inhibition was significantly enhanced. Compared with ordinary liposomes, this change was more significant in Der-loaded-pHSL. The uptake of pH-sensitive liposomes was higher in the simulated acidic tumour microenvironment, and the uptake showed a specific acid dependence. In vivo experiments showed that Der-loaded-pHSL had a significant tumour-targeting effect and could significantly enhance the antitumour effect of Dermaseptin-PP.

Conclusion

Der-loaded-pHSL designed in this study is a liposome with a quick, simple, effective preparation method, which can significantly reduce the haemolytic toxicity of Dermaseptin-PP and enhance its antitumour effect by increasing the tumour accumulation and cell intake. It provides a new idea for applying Dermaseptin-PP and other anticancer peptides with α-helical structure.

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来源期刊
IET nanobiotechnology
IET nanobiotechnology 工程技术-纳米科技
CiteScore
6.20
自引率
4.30%
发文量
34
审稿时长
1 months
期刊介绍: Electrical and electronic engineers have a long and illustrious history of contributing new theories and technologies to the biomedical sciences. This includes the cable theory for understanding the transmission of electrical signals in nerve axons and muscle fibres; dielectric techniques that advanced the understanding of cell membrane structures and membrane ion channels; electron and atomic force microscopy for investigating cells at the molecular level. Other engineering disciplines, along with contributions from the biological, chemical, materials and physical sciences, continue to provide groundbreaking contributions to this subject at the molecular and submolecular level. Our subject now extends from single molecule measurements using scanning probe techniques, through to interactions between cells and microstructures, micro- and nano-fluidics, and aspects of lab-on-chip technologies. The primary aim of IET Nanobiotechnology is to provide a vital resource for academic and industrial researchers operating in this exciting cross-disciplinary activity. We can only achieve this by publishing cutting edge research papers and expert review articles from the international engineering and scientific community. To attract such contributions we will exercise a commitment to our authors by ensuring that their manuscripts receive rapid constructive peer opinions and feedback across interdisciplinary boundaries. IET Nanobiotechnology covers all aspects of research and emerging technologies including, but not limited to: Fundamental theories and concepts applied to biomedical-related devices and methods at the micro- and nano-scale (including methods that employ electrokinetic, electrohydrodynamic, and optical trapping techniques) Micromachining and microfabrication tools and techniques applied to the top-down approach to nanobiotechnology Nanomachining and nanofabrication tools and techniques directed towards biomedical and biotechnological applications (e.g. applications of atomic force microscopy, scanning probe microscopy and related tools) Colloid chemistry applied to nanobiotechnology (e.g. cosmetics, suntan lotions, bio-active nanoparticles) Biosynthesis (also known as green synthesis) of nanoparticles; to be considered for publication, research papers in this area must be directed principally towards biomedical research and especially if they encompass in vivo models or proofs of concept. We welcome papers that are application-orientated or offer new concepts of substantial biomedical importance Techniques for probing cell physiology, cell adhesion sites and cell-cell communication Molecular self-assembly, including concepts of supramolecular chemistry, molecular recognition, and DNA nanotechnology Societal issues such as health and the environment Special issues. Call for papers: Smart Nanobiosensors for Next-generation Biomedical Applications - https://digital-library.theiet.org/files/IET_NBT_CFP_SNNBA.pdf Selected extended papers from the International conference of the 19th Asian BioCeramic Symposium - https://digital-library.theiet.org/files/IET_NBT_CFP_ABS.pdf
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