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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

Authors
HYESEON KIMYOUNG MIN SHINSeyong ChungDA HEE KIMPark D.B.SEWOOM BAEKJEONGGEUN PARKSIYEONG KIMKim D.-H.SE WON YISONGHYUN LEELee J.B.Ko J.-Y.Im G.-I.MI-LAN KANGHak-Joon Sung
Issue Date
Oct-2021
Publisher
WILEY-V C H VERLAG GMBH
Keywords
cell membranes; cell?cell packing; hypoxia; nanoparticles; Notch-1 aptamers
Citation
ADVANCED MATERIALS, v.33, no.40, pp.2,101,558
Journal Title
ADVANCED MATERIALS
Volume
33
Number
40
Start Page
2,101,558
URI
https://yscholarhub.yonsei.ac.kr/handle/2021.sw.yonsei/5269
DOI
10.1002/adma.202101558
ISSN
0935-9648
Abstract
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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