Affiliation:
1. Hospital of Stomatology Guanghua School of Stomatology Sun Yat‐sen University South China Center of Craniofacial Stem Cell Research Guangdong Provincial Key Laboratory of Stomatology Guangzhou 510055 China
2. School of Pharmaceutical Science (Shenzhen) Shenzhen Campus of Sun Yat‐sen University Shenzhen 518107 China
3. Stomatological Hospital School of Stomatology Southern Medical University Guangzhou 510055 China
4. Bioprocessing Technology Institute Agency for Science, Technology and Research (A*STAR) 20 Biopolis Way, Centros #06-01 Singapore 138669 Singapore
Abstract
AbstractExtracellular vesicles (EVs) are lipid bilayer nanovesicles released from living or apoptotic cells that can transport DNA, RNA, protein, and lipid cargo. EVs play critical roles in cell–cell communication and tissue homeostasis, and have numerous therapeutic uses including serving as carriers for nanodrug delivery. There are multiple ways to load EVs with nanodrugs, such as electroporation, extrusion, and ultrasound. However, these approaches may have limited drug‐loading rates, poor EV membrane stability, and high cost for large‐scale production. Here, it is shown that apoptotic mesenchymal stem cells (MSCs) can encapsulate exogenously added nanoparticles into apoptotic vesicles (apoVs) with a high loading efficiency. When nano‐bortezomib is incorporated into apoVs in culture‐expanded apoptotic MSCs, nano‐bortezomib‐apoVs show a synergistic combination effect of bortezomib and apoVs to ameliorate multiple myeloma (MM) in a mouse model, along with significantly reduced side effects of nano‐bortezomib. Moreover, it is shown that Rab7 regulates the nanoparticle encapsulation efficiency in apoptotic MSCs and that activation of Rab7 can increase nanoparticle‐apoV production. In this study, a previously unknown mechanism to naturally synthesize nano‐bortezomib‐apoVs to improve MM therapy is revealed.
Funder
National Natural Science Foundation of China
Agency for Science, Technology and Research
Subject
Biomaterials,Biotechnology,General Materials Science,General Chemistry
Cited by
3 articles.
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