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Exosome-loaded degradable polymeric microcapsules for the treatment of vitreoretinal diseases

Nature Biomedical Engineering (2023)Cite this article

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Abstract

The therapeutic benefits of many cell types involve paracrine mechanisms. Inspired by the paracrine functions of exosomes and the sustained degradation properties of microcapsules, here we report the therapeutic benefits of exosome-loaded degradable poly(lactic-co-glycolic acid) microcapsules with micrometric pores for the treatment of vitreoretinal diseases. On intravitreal injection in a mouse model of retinal ischaemia-reperfusion injury, microcapsules encapsulating mouse mesenchymal-stem-cell-derived exosomes settled in the inferior vitreous cavity, released exosomes for over one month as they underwent degradation and led to the restoration of retinal thickness to nearly that of the healthy retina. In mice and non-human primates with primed mycobacterial uveitis, intravitreally injected microcapsules loaded with exosomes from monkey regulatory T cells resulted in a substantial reduction in the levels of inflammatory cells. The exosome-encapsulating microcapsules, which can be lyophilised, may offer alternative treatment options for vitreoretinal diseases.

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Fig. 1: Construction and characterization of MExoCap.
Fig. 2: Protective effects of MExo released from MExoCap in the RIRI model in vitro.
Fig. 3: Intraocular retention, distribution and biological stability of MExoCap.
Fig. 4: Protective efficacy of MExoCap in a RIRI mouse model.
Fig. 5: Anti-inflammatory efficacy of TrExoCap in a PMU mouse model.
Fig. 6: Anti-inflammatory effects of TrExoCap in a PMU non-human primate model.

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Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. The RNA-sequencing data are available from the NCBI BioProject via the accession code PRJNA1000442. The mass spectrometry and proteomics data are available from the ProteomeXchange Consortium (through the iProX partner repository) via the dataset identifier PXD044401. Source data for the figures are provided with this paper, and are also available from figshare at https://doi.org/10.6084/m9.figshare.23849181.v1.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (T2225021 and U2001224 to W.W., 82070948 to Y. Tao, 32030062 to G.M. and 82101138 to Y. Tian), the Beijing Natural Science Foundation (JQ21027 to W.W.), the Shunyi District ‘Beijing science and technology achievements transformation coordination and service platform’ construction fund (SYGX202010 to Y. Tao) and the Beijing Hospitals Authority’s Ascent Plan (DFL20220301 to Y. Tao).

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  1. These authors contributed equally: Han Bao, Ying Tian.

Authors and Affiliations

  1. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China

    Han Bao, Ying Tian, Haixin Wang, Tong Ye, Shuang Wang, Jiawei Zhao, Guanghui Ma & Wei Wei

  2. Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P. R. China

    Han Bao, Ying Tian & Yong Tao

  3. School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, P. R. China

    Tong Ye, Guanghui Ma & Wei Wei

  4. Laboratory Animal Center of the Academy of Military Medical Sciences, Beijing, P. R. China

    Yefeng Qiu

  5. Department of Ophthalmology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China

    Jian Li

  6. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing, P. R. China

    Chao Pan

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Contributions

W.W., Y. Tao and G.M. conceived and designed the study. H.B. and Y. Tian performed most of the experiments and analysed the data. T.Y. and H.W. assisted with microcapsule preparation. S.W., J.Z. and J.L. provided suggestions about the project design and data presentation. Y.Q. and C.P. assisted with the experiment on cynomolgus monkeys. W.W., H.B. and Y. Tian wrote the original draft manuscript, and W.W., Y. Tao and G.M. revised the manuscript.

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Correspondence to Guanghui Ma, Wei Wei or Yong Tao.

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Nature Biomedical Engineering thanks Ke Cheng and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Bao, H., Tian, Y., Wang, H. et al. Exosome-loaded degradable polymeric microcapsules for the treatment of vitreoretinal diseases. Nat. Biomed. Eng (2023). https://doi.org/10.1038/s41551-023-01112-3

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