Cell-Membrane-Derived Nanoparticles with Notch-1 Suppressor Delivery Promote Hypoxic Cell-Cell Packing and Inhibit Angiogenesis Acting as a Two-Edged Sword
  • Kim, Hye-Seon
  • Shin, Young Min
  • Chung, Seyong
  • Kim, Dahee
  • Park, Dan Bi
  • ... Lee, Jung Bok
  • 외 10명
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초록

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.

키워드

cell membranescell-cell packinghypoxiananoparticlesNotch-1 aptamersTRANSCRIPTIONAL ACTIVATIONINDUCIBLE FACTORSGROWTH-FACTORSTEM-CELLCANCERCARTILAGEDIFFERENTIATIONCHONDROGENESISHIF-1-ALPHAMECHANISMS
제목
Cell-Membrane-Derived Nanoparticles with Notch-1 Suppressor Delivery Promote Hypoxic Cell-Cell Packing and Inhibit Angiogenesis Acting as a Two-Edged Sword
저자
Kim, Hye-SeonShin, Young MinChung, SeyongKim, DaheePark, Dan BiBaek, SewoomPark, JeongeunKim, Si YeongKim, Dae-HyunYi, Se WonLee, SonghyunLee, Jung BokKo, Ji-YunIm, Gun-IlKang, Mi-LanSung, Hak-Joon
DOI
10.1002/adma.202101558
발행일
2021-10
유형
Article
저널명
Advanced Materials
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