In Situ Cell Membrane Fusion for Engineered Tumor Cells by Worm-like Nanocell Mimics

Cell-based therapy is a promising clinic strategy to address many unmet medical needs. However, engineering cells faces some inevitable challenges, such as limited sources of cells, cell epigenetic alterations, and short shelf life during in vitro culture. Here, the worm-like nanocell mimics are fabricated to engineer effectively the tumor cells in vivo through the synergistic combination of nongenetic membrane surface engineering and inside encapsulation using in situ cell membrane fusion. The specific targeting and deformability of nanocell mimics play a vital role in membrane fusion mechanisms. The engineered primary tumor cells improved the tumor penetration of therapeutic cargoes via extracellular vesicles, while the engineered circulating tumor cells (CTCs) can capture the homologous cells to form the CTC clusters in the bloodstream and eliminate the CTC clusters in the lung, thus achieving excellent antitumor and antimetastasis efficacy. Above all, we find an intriguing phenomenon, in situ cell membrane fusion by the worm-like nanocell mimics, and our finding of in situ cell membrane fusion inspired us to engineer tumor cells in vivo. The present study would be a particularly meaningful strategy to directly engineer cells in vivo for cell-based therapy.