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Cell-Membrane-Derived Nanoparticles with Notch-1 Suppressor Delivery Promote Hypoxic Cell-Cell Packing and Inhibit Angiogenesis Acting as a Two-Edged Sword

 Hye-Seon Kim  ;  Young Min Shin  ;  Seyong Chung  ;  Dahee Kim  ;  Dan Bi Park  ;  Sewoom Baek  ;  Jeongeun Park  ;  Si Yeong Kim  ;  Dae-Hyun Kim  ;  Se Won Yi  ;  Songhyun Lee  ;  Jung Bok Lee  ;  Ji-Yun Ko  ;  Gun-Il Im  ;  Mi-Lan Kang  ;  Hak-Joon Sung 
 ADVANCED MATERIALS, Vol.33(40) : e2101558, 2021-10 
Journal Title
Issue Date
Notch-1 aptamers ; cell membranes ; cell-cell packing ; hypoxia ; nanoparticles
Cell-cell interactions regulate intracellular signaling via reciprocal contacts of cell membranes in tissue regeneration and cancer growth, indicating a critical need of membrane-derived tools in studying these processes. Hence, cell-membrane-derived nanoparticles (CMNPs) are produced using tonsil-derived mesenchymal stem cells (TMSCs) from children owing to their short doubling time. As target cell types, laryngeal cancer cells are compared to bone-marrow-derived MSCs (BMSCs) because of their cartilage damaging and chondrogenic characteristics, respectively. Treating spheroids of these cell types with CMNPs exacerbates interspheroid hypoxia with robust maintenance of the cell-cell interaction signature for 7 days. Both cell types prefer a hypoxic environment, as opposed to blood vessel formation that is absent in cartilage but is required for cancer growth. Hence, angiogenesis is inhibited by displaying the Notch-1 aptamer on CMNPs. Consequently, laryngeal cancer growth is suppressed efficiently in contrast to improved chondroprotection observed in a series of cell and animal experiments using a xenograft mouse model of laryngeal cancer. Altogether, CMNPs execute a two-edged sword function of inducing hypoxic cell-cell packing, followed by suppressing angiogenesis to promote laryngeal cancer death and chondrogenesis simultaneously. This study presents a previously unexplored therapeutic strategy for anti-cancer and chondroprotective treatment using CMNPs.
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1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Da Hee(김다희) ORCID logo https://orcid.org/0000-0001-7286-1334
Sung, Hak-Joon(성학준) ORCID logo https://orcid.org/0000-0003-2312-2484
Shin, Young Min(신영민)
Lee, Songhyun(이송현)
Chung, Seyong(정세용) ORCID logo https://orcid.org/0000-0001-9753-7055
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