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Endosome-triggered ion-releasing nanoparticles as therapeutics to enhance the angiogenic efficacy of human mesenchymal stem cells

Cited 2 time in Web of Science Cited 3 time in Scopus
Authors
Im, Gwang-Bum; Jung, Euiyoung; Kim, Yeong Hwan; Kim, Yu-Jin; Kim, Sung-Won; Jeong, Gun-Jae; Lee, Tae-Jin; Kim, Dong-Ik; Kim, Jinheung; Hyeon, Taeghwan; Yu, Taekyung; Bhang, Suk Ho
Issue Date
2020-08
Citation
Journal of Controlled Release, Vol.324, pp.586-597
Keywords
AngiogenesisCell homingEndosome-triggered nanoparticlesIntracellular ROS controlStem cell
Abstract
Here, we report that Fe ions delivered into human mesenchymal stem cells (hMSCs) by bioreducible metal nanoparticles (NPs) enhance their angiogenic and cell-homing efficacy by controlling ion-triggered intracellular reactive oxygen species (ROS) and improve cell migration, while reducing cytotoxicity. Endosome-triggered iron-ion-releasing nanoparticles (ETIN) were designed to be low-pH responsive to take advantage of the low-pH conditions (4-5) of endosomes for in situ iron-ion release. Due to the different redox potentials of Fe and Au, only Fe could be ionized and released from our novel ETIN, while Au remained intact after ETIN endocytosis. Treatment with an optimal amount of ETIN led to a mild increase in intracellular ROS levels in hMSCs, which enhanced the expression of HIF-1 alpha, a key trigger for angiogenic growth factor secretion from hMSCs. Treatmetn of hMSCs with ETIN significantly enhanced the expression of angiogenesis-and lesion-targeting-related genes and proteins. Transplantation of ETIN-treated hMSCs significantly enhanced angiogenesis and tissue regeneration in a wound-closing mouse model compared with those in untreated mice and mice that underwent conventional hMSC transplantation.
ISSN
0168-3659
URI
https://hdl.handle.net/10371/171755
DOI
https://doi.org/10.1016/j.jconrel.2020.05.038
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College of Engineering/Engineering Practice School (공과대학/대학원)Dept. of Chemical and Biological Engineering (화학생물공학부)Journal Papers (저널논문_화학생물공학부)
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