Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes

Abstract Background Efficient and topical delivery of drugs is essential for maximized efficacy and minimized toxicity. In this study, we aimed to design an exosome-based drug delivery platform endowed with the ability of escaping from phagocytosis at non-target organs and controllably releasing dru...

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Autores principales:	Yitong Guo, Zhuo Wan, Ping Zhao, Mengying Wei, Yunnan Liu, Te Bu, Wenqi Sun, Zhelong Li, Lijun Yuan
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Targeted drug delivery Exosomes Stealth technique Ultrasound Bmp7 White fat browning Biotechnology TP248.13-248.65 Medical technology R855-855.5
Acceso en línea:	https://doaj.org/article/1b1e9096a06840269603bf229f1531d2
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spelling	oai:doaj.org-article:1b1e9096a06840269603bf229f1531d22021-12-05T12:19:08ZUltrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes10.1186/s12951-021-01145-31477-3155https://doaj.org/article/1b1e9096a06840269603bf229f1531d22021-12-01T00:00:00Zhttps://doi.org/10.1186/s12951-021-01145-3https://doaj.org/toc/1477-3155Abstract Background Efficient and topical delivery of drugs is essential for maximized efficacy and minimized toxicity. In this study, we aimed to design an exosome-based drug delivery platform endowed with the ability of escaping from phagocytosis at non-target organs and controllably releasing drugs at targeted location. Results The swtichable stealth coat CP05-TK-mPEG was synthesized and anchored onto exosomes through the interaction between peptide CP05 and exosomal surface marker CD63. Chlorin e6 (Ce6) was loaded into exosomes by direct incubation. Controllable removal of PEG could be achieved by breaking thioketal (TK) through reactive oxygen species (ROS), which was produced by Ce6 under ultrasound irradiation. The whole platform was called SmartExo. The stealth effects were analyzed in RAW264.7 cells and C57BL/6 mice via tracing the exosomes. To confirm the efficacy of the engineered smart exosomes, Bone morphogenetic protein 7 (Bmp7) mRNA was encapsulated into exosomes by transfection of overexpressing plasmid, followed by stealth coating, with the exosomes designated as SmartExo@Bmp7. Therapeutic advantages of SmartExo@Bmp7 were proved by targeted delivering Bmp7 mRNA to omental adipose tissue (OAT) of obese C57BL/6 mice for browning induction. SmartExo platform was successfully constructed without changing the basic characteristics of exosomes. The engineered exosomes effectively escaped from the phagocytosis by RAW264.7 and non-target organs. In addition, the SmartExo could be uptaken locally on-demand by ultrasound mediated removal of the stealth coat. Compared with control exosomes, SmartExo@Bmp7 effectively delivered Bmp7 mRNA into OAT upon ultrasound irradiation, and induced OAT browning, as evidenced by the histology of OAT and increased expression of uncoupling protein 1 (Ucp1). Conclusions The proposed SmartExo-based delivery platform, which minimizes side effects and maximizing drug efficacy, offers a novel safe and efficient approach for targeted drug delivery. As a proof, the SmartExo@Bmp7 induced local white adipose tissue browning, and it would be a promising strategy for anti-obesity therapy. Graphical AbstractYitong GuoZhuo WanPing ZhaoMengying WeiYunnan LiuTe BuWenqi SunZhelong LiLijun YuanBMCarticleTargeted drug deliveryExosomesStealth techniqueUltrasoundBmp7White fat browningBiotechnologyTP248.13-248.65Medical technologyR855-855.5ENJournal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Targeted drug delivery Exosomes Stealth technique Ultrasound Bmp7 White fat browning Biotechnology TP248.13-248.65 Medical technology R855-855.5
spellingShingle	Targeted drug delivery Exosomes Stealth technique Ultrasound Bmp7 White fat browning Biotechnology TP248.13-248.65 Medical technology R855-855.5 Yitong Guo Zhuo Wan Ping Zhao Mengying Wei Yunnan Liu Te Bu Wenqi Sun Zhelong Li Lijun Yuan Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes
description	Abstract Background Efficient and topical delivery of drugs is essential for maximized efficacy and minimized toxicity. In this study, we aimed to design an exosome-based drug delivery platform endowed with the ability of escaping from phagocytosis at non-target organs and controllably releasing drugs at targeted location. Results The swtichable stealth coat CP05-TK-mPEG was synthesized and anchored onto exosomes through the interaction between peptide CP05 and exosomal surface marker CD63. Chlorin e6 (Ce6) was loaded into exosomes by direct incubation. Controllable removal of PEG could be achieved by breaking thioketal (TK) through reactive oxygen species (ROS), which was produced by Ce6 under ultrasound irradiation. The whole platform was called SmartExo. The stealth effects were analyzed in RAW264.7 cells and C57BL/6 mice via tracing the exosomes. To confirm the efficacy of the engineered smart exosomes, Bone morphogenetic protein 7 (Bmp7) mRNA was encapsulated into exosomes by transfection of overexpressing plasmid, followed by stealth coating, with the exosomes designated as SmartExo@Bmp7. Therapeutic advantages of SmartExo@Bmp7 were proved by targeted delivering Bmp7 mRNA to omental adipose tissue (OAT) of obese C57BL/6 mice for browning induction. SmartExo platform was successfully constructed without changing the basic characteristics of exosomes. The engineered exosomes effectively escaped from the phagocytosis by RAW264.7 and non-target organs. In addition, the SmartExo could be uptaken locally on-demand by ultrasound mediated removal of the stealth coat. Compared with control exosomes, SmartExo@Bmp7 effectively delivered Bmp7 mRNA into OAT upon ultrasound irradiation, and induced OAT browning, as evidenced by the histology of OAT and increased expression of uncoupling protein 1 (Ucp1). Conclusions The proposed SmartExo-based delivery platform, which minimizes side effects and maximizing drug efficacy, offers a novel safe and efficient approach for targeted drug delivery. As a proof, the SmartExo@Bmp7 induced local white adipose tissue browning, and it would be a promising strategy for anti-obesity therapy. Graphical Abstract
format	article
author	Yitong Guo Zhuo Wan Ping Zhao Mengying Wei Yunnan Liu Te Bu Wenqi Sun Zhelong Li Lijun Yuan
author_facet	Yitong Guo Zhuo Wan Ping Zhao Mengying Wei Yunnan Liu Te Bu Wenqi Sun Zhelong Li Lijun Yuan
author_sort	Yitong Guo
title	Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes
title_short	Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes
title_full	Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes
title_fullStr	Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes
title_full_unstemmed	Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes
title_sort	ultrasound triggered topical delivery of bmp7 mrna for white fat browning induction via engineered smart exosomes
publisher	BMC
publishDate	2021
url	https://doaj.org/article/1b1e9096a06840269603bf229f1531d2
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Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes

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