Curcumin exerts therapeutic effects in heart disease, but has limited bioavailability. Extracellular vesicles (EVs) have gained attention as nanovehicles; however, the poor targeting ability of systemically administered EVs still remains a crucial issue. Herein, we generated heart-targeted EVs (CTP-EVs) by functionalizing EVs surface with cardiac targeting peptide (CTP) using genetic modification of EVs-secreting cells, and further loaded curcumin into CTP-EVs (CTP-EVs-Cur). Consequently, CTP-EVs were able to specifically deliver curcumin to the heart. In addition, curcumin-loaded CTP-EVs possess improved bioavailability, and are fully functional with a high cardioprotective efficiency. Moreover, we loaded miR-144-3p in CTP-EVs-Cur following validation of miR-144-3p as a major contributor in curcumin-mediated therapeutic effects. The simultaneous packing of curcumin and miR-144-3p in CTP-EVs not only retains the active heart-targeting ability but also achieves enhanced cardioprotective effects both in vitro and in vivo, indicating the possibility of combining and sustaining their therapeutic potential by simultaneously loading in CTP-EVs. Therefore, CTP-EVs could be a potential and effective strategy for the delivery of therapeutic molecules, thereby providing a promising nanomedicine for MI therapy.
Bibliographical noteFunding Information:
This study was supported by research grants from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (NRF- 2017R1A2B3003303 ), the Korean Healthcare Technology R&D project funded by the Ministry of Health & Welfare ( HI16C0058 ), and the CMB-Yuhan research grant of Yonsei University College of Medicine ( 6-2019-0124 ). Also, this study was partially supported by the Graduate School of YONSEI University Research Scholarship Grants in 2020. The authors would like to thank Editage ( www.editage.co.kr ) for english language editing. We also thank Medical Illustration & Design, part of the Medical Research Support Services of Yonsei University College of Medicine, for all artistic support related to this work.
© 2021 Elsevier B.V.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science