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In Situ Reprogrammings of Splenic CD11b+ Cells by Nano-Hypoxia to Promote Inflamed Damage Site-Specific Angiogenesis

 Seyong Chung  ;  Si Yeong Kim  ;  Kyubae Lee  ;  Sewoom Baek  ;  Hyun-Su Ha  ;  Dae-Hyun Kim  ;  Suji Park  ;  Chan Hee Lee  ;  Hye-Seon Kim  ;  Young Min Shin  ;  Seung Eun Yu  ;  Hak-Joon Sung 
 ADVANCED FUNCTIONAL MATERIALS, Vol.33(32) : 2302817, 2023-08 
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Clinical translation of nanoparticles is limited because of their short circulation time, which hampers targeting to prolong therapeutic effects. Angiogenesis is required to regenerate damaged sites under inflammation, and CD11b+ cells turn vasculogenic under hypoxia. As a turning-point strategy to increase the circulation time, this study explores liposomal targeting of splenic CD11b+ cells, which are gathered in the spleen and move to inflamed sites inherently. Moreover, nano-hypoxia is strategized as a therapeutic method by loading liposomes with a hypoxic-mimetic agent (CoCl2) to induce in situ reprogramming of splenic CD11b+ cells upon venous injection. Consequently, the vasculogenic potential of reprogrammed cells accelerates regeneration through inflammation-responsive homing. Hydrophilic coating of liposomes improves the selectivity of splenic targeting in contrast to fast targeting without coating. Hypoxia chambers and surgical induction of splenic hypoxia are compared to validate the reprogramming effect. The strategy is validated in mouse models of inflamed skin, ischemic hindlimbs, and 70% hepatectomy compared with a conventional approach using bone marrow cells. Intravital multiphoton microscopy, 19F 2D/3D MRI, and microchannel hydrogel chips for 3D tissue culture are used as advanced tools. Overall, nanocarrier change to CD11b+ cells prolong targeting by inducing in situ reprogramming for inflammation-responsive vasculogenic therapy.
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1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
Yonsei Authors
Sung, Hak-Joon(성학준) ORCID logo https://orcid.org/0000-0003-2312-2484
Shin, Young Min(신영민)
Yu, Seung Eun(유승은) ORCID logo https://orcid.org/0000-0002-9690-8739
Lee, Kyubae(이규배) ORCID logo https://orcid.org/0000-0002-1270-8554
Chung, Seyong(정세용) ORCID logo https://orcid.org/0000-0001-9753-7055
Ha, Hyun-Su(하현수)
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