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基于表面修饰的空泡递药系统用于急性髓细胞白血病(AML)及其选择性治疗。

Surface-modified vacuole-based daunorubicin delivery system for acute myeloid leukaemia (AML) and their selective therapeutics.

机构信息

Graduate School of Semiconductor and Chemical Engineering, Jeonbuk National University, Jeonbuk, South Korea.

School of Biological Sciences, Chungbuk National University, Cheongju, South Korea.

出版信息

Artif Cells Nanomed Biotechnol. 2022 Dec;50(1):147-157. doi: 10.1080/21691401.2022.2078339.

Abstract

The vacuoles in are the key players digesting the waste within the cell. This functional organelle corresponding to the lysosome of mammalians contains acidic hydrolases and specific membrane proteins. Vacuoles have more than 60 hydrolytic enzymes and can easily be modified by genetic engineering. In previous study, we optimised the encapsulation condition with appropriate time and concentration and confirmed the use of vacuole as drug delivery carrier for acute myeloid leukaemia treatment. In this study, recombinant vacuole that could target the acute myeloid leukaemia cell line was constructed. The vacuoles derived from genetic engineered yeast were decorated with targeting peptide that has specific affinity with TLR2 on AML cell membrane. The anti-cancer efficacy of AML targeting vacuoles carriers with encapsulated daunorubicin was shown to be higher than normal vacuole carriers and the crude daunorubicin. The results confirmed that target selective chemotherapy using the vacuole drug delivery system is effective and offers potential for cancer therapy.

摘要

细胞内的空泡是消化细胞内废物的关键角色。这个功能细胞器对应于哺乳动物的溶酶体,包含酸性水解酶和特定的膜蛋白。空泡含有超过 60 种水解酶,并且很容易通过基因工程进行修饰。在之前的研究中,我们优化了包封条件,包括适当的时间和浓度,并确认了空泡作为急性髓系白血病治疗的药物递送载体的用途。在本研究中,构建了能够靶向急性髓系白血病细胞系的重组空泡。从基因工程酵母中衍生的空泡被靶向肽修饰,该靶向肽与 AML 细胞膜上的 TLR2 具有特异性亲和力。用包封的柔红霉素的 AML 靶向空泡载体的抗癌功效明显高于普通空泡载体和粗制柔红霉素。结果证实,使用空泡药物递送系统进行靶向选择性化疗是有效的,并为癌症治疗提供了潜力。

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