Page 236 - ebook

[D. Medicine/Translational Research] D-2

Notch-1 suppressor conjugated Cell membrane-derived

nanoparticles promote hypoxic cell–cell packing and suppress

angiogenesis as a two-edged sword

#
Hye-Seon Kim¹ , Young Min Shin¹ , Seyong Chung¹, Dan Bi Park², Sewoom Baek¹, Jeongeun Park¹, Si
#
Yeong Kim¹, Dae-Hyun Kim³, Se Won Yi², Songhyun Lee¹, Jung Bok Lee⁴, Seong Mi Yu¹, Hyun-Su Ha¹,
Chan Hee Lee¹, Mi-Lan Kang²*, Hak-Joon Sung¹*

¹Department of Medical Engineering, Yonsei University College of Medicine, Seoul 03722, Korea, ²TMD LAB Co.,
Ltd, TMD LAB Co., Ltd, Seoul 04799, Korea, ³Department of Veterinary Surgery, Chungnam National University

College of Veterinary Medicine, Daejeon 34134, Korea, ⁴Department of Biological Science, Sookmyung Women’s
University, Seoul 04310, Korea

Cell–cell interactions regulate intracellular signaling for tissue regeneration and cancer growth. Because the cell
membrane is a key regulator of this process, there is an unmet need to employ a membrane-derived tool to study

cell–cell interactions. Hence, cell membrane-derived nanoparticles (CMNPs) were produced using tonsil-derived
mesenchymal stem cells (TMSCs) from children owing to their efficient cell growth and short doubling time. As
target cell types, laryngeal cancer cells were compared to bone marrow-derived MSCs (BMSCs) because of their

cartilage-damageable and chondrogenic characteristics, respectively. When CMNPs treated in spheroids of these

cell types, the exacerbating internal hypoxia of spheroid and robust maintenance of the cell–cell interaction signature
were observed during the 7-day culture. Hypoxia represents a common environmental preference of both cell types
as opposed to angiogenesis, which is absent in cartilage but is required for cancer growth. Hence, angiogenesis

was inhibited by conjugating the Notch-1 antagonistic aptamer on CMNPs. Consequently, laryngeal cancer growth

was suppressed efficiently in contrast to clear improvement of protecting cartilage, as seen in a series of in vitro
and in vivo experiments with a xenograft mouse model of laryngeal cancer. This study presents a new perspective
for using CMNPs as a previously unexplored therapeutic strategy.