Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes
Open accessAbstract
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:
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CP05-TK-mPEG switchable stealth core-decorating exosomes loaded with Ce6 and Bmp7 mRNA can locally degrade by ultrasound, resulting in precise delivery of Bmp7 mRNA to omental adipose tissue of obese mice.
“CP05-TK-mPEG switchable stealth core-decorating exosomes were developed and loaded with Chlorin e6 (Ce6) and bone Bmp7 mRNA. This smart system can locally degrade by ultrasound (US), resulting in precise delivery of Bmp7 mRNA to the omental adipose tissue (OAT) of obese mice (Fig. 4) [97].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [97]
Localized US-assisted delivery of Bmp7 using decorated exosomes elicited efficient browning of OAT and proved promising anti-obesity therapy.
“The study results revealed that localized US-assisted delivery of Bmp7 elicited efficient browning of OAT and proved as a promising anti-obesity therapy [97].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [97]
SmartExo@Bmp7 induced local white adipose tissue browning through transporting Bmp7 mRNA to reduce obesity for C57BL/6 mice.
“This biological system induced local white adipose tissue browning through transporting Bmp7 mRNA to reduce obesity for C57BL/6 mice.”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [111]
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Liu, Q., Li, D., Pan, X., & Liang, Y. (2023) · Journal of Nanobiotechnology · doi:10.1186/s12951-023-02081-0 · Cited by 201 · see citing works
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- Authors
- Guo, Y., Wan, Z., Zhao, P., Wei, M., Liu, Y., Bu, T., Sun, W., Li, Z., & Yuan, L.
- Affiliations
- Tang Du Hospital (CN)
- State Key Laboratory of Cancer Biology (CN)
- Corresponding author
- Yuan, Lijun
- Venue
- Journal of Nanobiotechnology
- Published
- 2021-12
- Volume
- 19
- Issue
- 1
- Pages
- 402-402
- ISSN
- 1477-3155 (ISSN-L)
- PMC
- PMC8645082
- OpenAlex
- W4200596304
- Cited by
- 60
- References
- 41
- Citations by year
- 2026: 14 · 2025: 15 · 2024: 14 · 2023: 11 · 2022: 6
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Nanobiotechnology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81871357, 81671690)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- engineered exosomes, ultrasound-triggered drug release, white adipose tissue browning, obesity treatment, stealth coatings, chlorin e6, reactive oxygen species, UCP1, topical drug delivery, omental adipose tissue
- MeSH terms
- RAW 264.7 Cells, Administration, Topical, Animals, Adipose Tissue, Brown, Male, Mice, Inbred C57BL, RNA, Messenger, Ultrasonic Therapy, Drug Delivery Systems, Mice, Adipose Tissue, White, Exosomes, Bone Morphogenetic Protein 7, Bioengineering
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