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

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.