Full Text | PDF

Theranostics 2020; 10(7):3240-3253. doi:10.7150/thno.39870 This issue Cite

Research Paper

Development of microRNA-21 mimic nanocarriers for the treatment of cutaneous wounds

Sun Young Wang^1,2*, Hyosuk Kim^1,2*, Gijung Kwak^1,2, Sung Duk Jo¹, Daeho Cho³, Yoosoo Yang¹, Ick Chan Kwon^1,2, Ji Hoon Jeong^4✉, Sun Hwa Kim^1✉

1. Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
2. KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea.
3. Nano-Bio Resources Center, Korea University, Seoul 02841, Republic of Korea.
4. School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
*These authors contributed equally to this work.

✉ Corresponding authors: jhjeongedu (J.H.J.); sunkimre.kr (S.H.K.).

Abstract

Rationale: Of the regulatory microRNAs expressed in the wounded skin, microRNA-21 (miR21) plays a pivotal role in wound repair by stimulating re-epithelialization, an essential feature to facilitate healing and reduce scar formation. Despite their crucial roles in wound healing, synthetic exogenous microRNAs have limited applications owing to the lack of an appropriate delivery system. Herein, we designed an miR21 mimic nanocarrier system using facial amphipathic bile acid-conjugated polyethyleneimines (BA-PEI) for the intracellular and transdermal delivery of synthetic miR21 molecules to accelerate wound repair.

Methods: To design miR21 mimic nanocarriers, BA-conjugated PEIs prepared from three different types of BA at molar feed ratios of 1 and 3 were synthesized. The intracellular uptake efficiency of synthetic miR21 mimics was studied using confocal laser scanning microscopy and flow cytometry analysis. The optimized miR21/BA nanocarrier system was used to evaluate the wound healing effects induced by miR21 mimics in human HaCaT keratinocytes in vitro and a murine excisional acute wound model in vivo.

Results: The cell uptake efficiency of miR21 complexed with BA-conjugated PEI was dramatically higher than that of miR21 complexed with PEI alone. Deoxycholic acid (DA)-modified PEI at a molar feed ratio of 3:1 (DA3-PEI) showed the highest transfection efficiency for miR21 without any increase in toxicity. After effective transdermal and intracellular delivery of miR21/DA3 nanocarriers, miR21 mimics promoted cell migration and proliferation through the post-transcriptional regulation of programmed cell death protein 4 (PDCD4) and matrix metalloproteinases. Thus, miR21 mimic nanocarriers improved both the rate and quality of wound healing, as evident from enhanced collagen synthesis and accelerated wound re-epithelialization.

Conclusion: Our miRNA nanocarrier systems developed using DA3-PEI conjugates may be potentially useful for the delivery of synthetic exogenous miRNAs in various fields.

Keywords: microRNA-21, facial amphipathic bile acid, wound healing, gene therapy

Citation styles

©2024 Ivyspring International Publisher. Terms of use