Reversing the surface charge of MSC-derived small extracellular vesicles by epsilonPL-PEG-DSPE for enhanced osteoarthritis treatment


Posted: 2021-11-01 19:00:00
J Extracell Vesicles . 2021 Nov;10(13):e12160. doi: 10.1002/jev2.12160. Affiliations Expand Affiliations 1 Institute of Microsurgery on Extremities, Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. 2 Chemical and Environmental Engineering, School of Engineering, RMIT University, Melbourne, Australia. Item in Clipboard Kai Feng et al. J Extracell Vesicles. 2021 Nov. Show details Display options Display options Format J Extracell Vesicles . 2021 Nov;10(13):e12160. doi: 10.1002/jev2.12160. Affiliations 1 Institute of Microsurgery on Extremities, Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. 2 Chemical and Environmental Engineering, School of Engineering, RMIT University, Melbourne, Australia. Item in Clipboard CiteDisplay options Display options Format Abstract Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) possess a great therapeutical potential for osteoarthritis (OA) treatment. However, the steric and electrostatic hindrance of cartilage matrix leads to very limited distribution of MSC-sEVs in cartilage and low bioavailability of MSC-sEVs after intra-articular injection. To overcome this, a strategy to reverse the surface charge of MSC-sEVs by modifying the MSC-sEVs with a novel cationic amphiphilic macromolecule namely ε-polylysine-polyethylene-distearyl phosphatidylethanolamine (PPD) was developed in this study. Through incubation with 100 μg/ml PPD, positively charged MSC-sEVs (PPD-sEVs) were obtained, and the modification process showed nearly no disturbance to the integrity and contents of sEVs and exhibited good stability under the interference of anionic macromolecules. A more effective cellular uptake and homeostasis modulation ability of PPD-sEVs than unmodified MSC-sEVs to chondrocytes was demonstrated. More importantly, PPD-sEVs demonstrated significantly enhanced cartilage uptake, cartilage penetration, and joint retention capacity as compared to MSC-sEVs. Intra-articular injection of PPD-sEVs into a mouse OA model showed significantly improved bioavailability than MSC-sEVs, which resulted in enhanced therapeutic efficacy with reduced injection frequency. In general, this study provides a facile and effective strategy to improve the intra-articular bioavailability of MSC-sEVs and has a great potential to accelerate the clinical practice of MSC-sEVs based OA therapy. Keywords: MSC derived small extracellular vesicles; osteoarthritis; surface charge reverse; surface modification. © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. References REFERENCES Ahern, B. J., Parvizi, J., Boston, R., & Schaer, T. P. (2009). Preclinical animal models in single site cartilage defect testing: A systematic review. Osteoarthritis and Cartilage 17, 705-713. Arra, M., Swarnkar, G., Ke, K., Otero, J., Ying, J., Duan, X., Maruyama, T., Rai, M., O'Keefe, R., Mbalaviele, G., Shen, J., & Abu-Amer, Y. (2020). LDHA-mediated ROS generation in chondrocytes is a potential therapeutic target for osteoarthritis. Nature Communications 11, 3427. Bajpayee, A. G., & Grodzinsky, A. J. (2017). Cartilage-targeting drug delivery: Can electrostatic interactions help? Nature Reviews Rheumatology 13, 183-193. Bajpayee, A. G., Wong, C. R., Bawendi, M. G., Frank, E. H., & Grodzinsky, A. J. (2014). Avidin as a model for charge driven transport into cartilage and drug delivery for treating early stage post-traumatic osteoarthritis. Biomaterials 35, 538-549. Bankar, S. B., & Singhal, R. S. (2013). Panorama of poly-ε-lysine. RSC Advances 3, 8586-8603. Show all 65 references Grant support [x] Cite Copy Format: Send To [x]

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バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
1月 22, 2019 バイオアソシエイツ

化学療法は乳癌細胞から転移促進エキソソームの放出を刺激し、エクソソームはその内容物を肺に放出することがある。

乳癌患者の中には、腫瘍が手術で取り除かれる前に化学療法を受ける人もいる。 ネオアジュバント療法と呼ばれるこのアプローチは、乳房温存手術を容易にするために腫瘍のサイズを縮小するのを助け、外科医が除去するための癌性細胞をほとんどまたは全く残さずに腫瘍を根絶することさえできる。 そのような場合、患者は手術後の生涯に渡り癌のないまま過ごせる可能性が高い。 しかし、すべての腫瘍が化学療法で縮小するわけではない。…

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