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

Abstract 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 be...

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Autores principales: Yutaro Kase, Katsuhiro Uzawa, Sho Wagai, Shusaku Yoshimura, Jun-Ichiro Yamamoto, Yuriko Toeda, Megumi Okubo, Keitaro Eizuka, Toshiaki Ando, Takafumi Nobuchi, Kohei Kawasaki, Tomoaki Saito, Manabu Iyoda, Dai Nakashima, Atsushi Kasamatsu, Hideki Tanzawa
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/9ed74c814c914ce78df8087aa1a83150
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spelling oai:doaj.org-article:9ed74c814c914ce78df8087aa1a831502021-12-02T17:05:11ZEngineered exosomes delivering specific tumor-suppressive RNAi attenuate oral cancer progression10.1038/s41598-021-85242-12045-2322https://doaj.org/article/9ed74c814c914ce78df8087aa1a831502021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85242-1https://doaj.org/toc/2045-2322Abstract 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.Yutaro KaseKatsuhiro UzawaSho WagaiShusaku YoshimuraJun-Ichiro YamamotoYuriko ToedaMegumi OkuboKeitaro EizukaToshiaki AndoTakafumi NobuchiKohei KawasakiTomoaki SaitoManabu IyodaDai NakashimaAtsushi KasamatsuHideki TanzawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yutaro Kase
Katsuhiro Uzawa
Sho Wagai
Shusaku Yoshimura
Jun-Ichiro Yamamoto
Yuriko Toeda
Megumi Okubo
Keitaro Eizuka
Toshiaki Ando
Takafumi Nobuchi
Kohei Kawasaki
Tomoaki Saito
Manabu Iyoda
Dai Nakashima
Atsushi Kasamatsu
Hideki Tanzawa
Engineered exosomes delivering specific tumor-suppressive RNAi attenuate oral cancer progression
description Abstract 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.
format article
author Yutaro Kase
Katsuhiro Uzawa
Sho Wagai
Shusaku Yoshimura
Jun-Ichiro Yamamoto
Yuriko Toeda
Megumi Okubo
Keitaro Eizuka
Toshiaki Ando
Takafumi Nobuchi
Kohei Kawasaki
Tomoaki Saito
Manabu Iyoda
Dai Nakashima
Atsushi Kasamatsu
Hideki Tanzawa
author_facet Yutaro Kase
Katsuhiro Uzawa
Sho Wagai
Shusaku Yoshimura
Jun-Ichiro Yamamoto
Yuriko Toeda
Megumi Okubo
Keitaro Eizuka
Toshiaki Ando
Takafumi Nobuchi
Kohei Kawasaki
Tomoaki Saito
Manabu Iyoda
Dai Nakashima
Atsushi Kasamatsu
Hideki Tanzawa
author_sort Yutaro Kase
title Engineered exosomes delivering specific tumor-suppressive RNAi attenuate oral cancer progression
title_short Engineered exosomes delivering specific tumor-suppressive RNAi attenuate oral cancer progression
title_full Engineered exosomes delivering specific tumor-suppressive RNAi attenuate oral cancer progression
title_fullStr Engineered exosomes delivering specific tumor-suppressive RNAi attenuate oral cancer progression
title_full_unstemmed Engineered exosomes delivering specific tumor-suppressive RNAi attenuate oral cancer progression
title_sort engineered exosomes delivering specific tumor-suppressive rnai attenuate oral cancer progression
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/9ed74c814c914ce78df8087aa1a83150
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