Engineered exosomes delivering specific tumor-suppressive RNAi attenuate oral cancer progression.

Engineered exosomes delivering specific tumor-suppressive RNAi attenuate oral cancer progression.
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DOI:
10.1038/s41598-021-85242-1
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发表时间:
2021-03-15
期刊:
影响因子:
4.6
通讯作者:
Tanzawa H
Tanzawa H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kase Y;Uzawa K;Wagai S;Yoshimura S;Yamamoto JI;Toeda Y;Okubo M;Eizuka K;Ando T;Nobuchi T;Kawasaki K;Saito T;Iyoda M;Nakashima D;Kasamatsu A;Tanzawa H

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外泌体参与人类细胞中广泛的生物学过程。相当多的证据表明,含有治疗剂的工程化外泌体(eExosomes)可以减弱人癌细胞的致癌活性。尽管其具有生物医学相关性,但没有关于口腔鳞状细胞癌(OSCC)的信息,因此迫切需要开发特异性OSCC靶向eExosomes(octExosomes)。我们证明了用淋巴细胞胞质蛋白1(LCP 1)的siRNA电穿孔来自用EB病毒诱导的3(EBI 3)cDNA转染的正常成纤维细胞的外泌体,作为octExosomes,并进行一系列实验以评估施用octExosomes后的负载特异性/有效性及其抗口腔癌细胞活性。这些实验表明,octExosomes是稳定的,可以有效地将siLCP 1转移到OSCC细胞中,并且与其对应物相比,octExosomes在OSCC细胞中的LCP 1下调,从而在体外和体内产生显着的肿瘤抑制作用。在这里,我们报告了一种新的有价值的抑制肿瘤细胞的工具的发展。通过改造exosomes,siLCP 1被转移到特异性抑制OSCC细胞的致癌活性。抑制其他类型的人类恶性细胞值得进一步研究。
Exosomes are involved in a wide range of biological processes in human cells. Considerable evidence suggests that engineered exosomes (eExosomes) containing therapeutic agents can attenuate the oncogenic activity of human cancer cells. Despite its biomedical relevance, no information has been available for oral squamous cell carcinoma (OSCC), and therefore the development of specific OSCC-targeting eExosomes (octExosomes) is urgently needed. We demonstrated that exosomes from normal fibroblasts transfected with Epstein–Barr Virus Induced-3 (EBI3) cDNA were electroporated with siRNA of lymphocyte cytoplasmic protein 1 (LCP1), as octExosomes, and a series of experiments were performed to evaluate the loading specificity/effectiveness and their anti-oral cancer cell activities after administration of octExosomes. These experiments revealed that octExosomes were stable, effective for transferring siLCP1 into OSCC cells and LCP1 was downregulated in OSCC cells with octExosomes as compared with their counterparts, leading to a significant tumor-suppressive effect in vitro and in vivo. Here we report the development of a new valuable tool for inhibiting tumor cells. By engineering exosomes, siLCP1 was transferred to specifically suppress oncogenic activity of OSCC cells. Inhibition of other types of human malignant cells merits further study.
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