Efficient, High-Quality Engineering of Therapeutic Extracellular Vesicles on an Integrated Nanoplatform
Engineered extracellular vesicles (EVs) have been recognized as important therapeutics for gene and cell therapy. To achieve clinically desired therapy, technologies for EV engineering have high demands on the efficacy in producing EVs and their qualities, which, however, remain challenging to conventional routes due to their limited control on therapeutic payload delivery, EV secretion, and extracellular microenvironments. Here, we report a nanoplatform (denoted as PURE) that enables efficient electro-transfection while stimulating cells to produce high-quality EVs carrying functional RNAs. PURE further employs an ammonium removal zone to maintain the physiological conditions of the extracellular microenvironment and an EV uptake zone that efficiently (87.1%) captures EVs in situ with porous hydrogels. The platform achieved about a 12-fold higher yield of engineered EVs and a 146-fold abundance of desired therapeutics compared to those naturally secreted from cells. The PURE-engineered miR-130a-EVs were validated for effectively upregulating the mTOR signaling pathway in both in vitro and in vivo. Their therapeutic capability was then verified by enhancing the in vitro activation of primordial follicles. In vivo applications further highlighted the therapeutic effects of miR-130a-EVs in restoring ovary function in aged mice. The PURE platform represents a strategy for the clinical translation of EV-mediated therapy.
Authors
- Xinge Yu (ORCID: https://orcid.org/0000-0003-0522-1171)
- Dedong Yin
- Mingzhu Yang (ORCID: https://orcid.org/0000-0002-5484-0836)
- Xinran Jiang
- Hong Sun (ORCID: https://orcid.org/0000-0001-6799-6015)
- Lingqian Chang (ORCID: https://orcid.org/0000-0002-6329-9850)
- Zhaojian Liu (ORCID: https://orcid.org/0000-0002-2542-0859)
- Zixiang Wang (ORCID: https://orcid.org/0000-0001-5252-9764)
- Yuanyuheng Wang (ORCID: https://orcid.org/0000-0003-3863-5880)
- Han Wu (ORCID: https://orcid.org/0009-0006-9318-4436)
- Yongyan Hu
- Long Lin (ORCID: https://orcid.org/0000-0001-9123-5208)
- Mu Wei (ORCID: https://orcid.org/0000-0001-6365-1060)
- Ao Xiao
- Lamei Du (ORCID: https://orcid.org/0000-0002-3990-0183)
- Xing Chen (ORCID: https://orcid.org/0000-0001-7746-846X)
- Jiaqi Liu (ORCID: https://orcid.org/0000-0002-9775-2342)
- Feng Liu (ORCID: https://orcid.org/0000-0001-9560-8518)
- Kun Song (ORCID: https://orcid.org/0000-0001-6110-2770)
- Zhiyuan Jin
- Jiazheng Sun (ORCID: https://orcid.org/0009-0004-7114-5378)
- Zhaocun Huang
- Kuan Yang (ORCID: https://orcid.org/0009-0008-9804-586X)
- Shenshen Kong
- Yusen Wang (ORCID: https://orcid.org/0009-0007-5547-7163)
- Yibo Wang (ORCID: https://orcid.org/0009-0005-3781-5750)
Institutions
- Shandong University (CN)
- City University of Hong Kong (HK)
- Capital Medical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking University (CN)
- Third Affiliated Hospital of Guangzhou Medical University (CN)
- Beijing Chest Hospital (CN)
- Beijing Research Institute of Mechanical and Electrical Technology (CN)
- Peking University First Hospital (CN)
- Beihang University (CN)
- Ministry of Industry and Information Technology (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- ACS Nano
- Published
- 2024-10-25
- DOI
- https://doi.org/10.1021/acsnano.4c04730
- Citations
- 13
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 3.04
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China