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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., (© 2021 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Clinical translation of nanoparticles is limited because of their short circulation time, which hampers targeting to prolong therapeutic effects. Angiogenesis is required to regenerate damaged sites under inflammation, and CD11b+ cells turn vasculogenic under hypoxia. As a turning‐point strategy to increase the circulation time, this study explores liposomal targeting of splenic CD11b+ cells, which are gathered in the spleen and move to inflamed sites inherently. Moreover, nano‐hypoxia is strategized as a therapeutic method by loading liposomes with a hypoxic‐mimetic agent (CoCl2) to induce in situ reprogramming of splenic CD11b+ cells upon venous injection. Consequently, the vasculogenic potential of reprogrammed cells accelerates regeneration through inflammation‐responsive homing. Hydrophilic coating of liposomes improves the selectivity of splenic targeting in contrast to fast targeting without coating. Hypoxia chambers and surgical induction of splenic hypoxia are compared to validate the reprogramming effect. The strategy is validated in mouse models of inflamed skin, ischemic hindlimbs, and 70% hepatectomy compared with a conventional approach using bone marrow cells. Intravital multiphoton microscopy, 19F 2D/3D MRI, and microchannel hydrogel chips for 3D tissue culture are used as advanced tools. Overall, nanocarrier change to CD11b+ cells prolong targeting by inducing in situ reprogramming for inflammation‐responsive vasculogenic therapy. [ABSTRACT FROM AUTHOR]