Among biological membrane transport systems, endocytosis 55-60 is a universal cellular process in which a variety of extracellular substances, ranging from small biomolecules to micrometer-size substances that interact with the cell surface, are taken up via outsidein vesicle fission. Endocytic vesicle fission is closely associated with viral infection, signal transduction in neurons, 57,58 and phagocytosis associated with immune responses. In cellular endocytosis, biomolecular machines hybridized with cellular membranes enable the uptake of external substances in conjunction with outside-in vesicle fission. However, a molecular approach that enables endocytosis-like transport where membrane deformation is synchronized with substance transport remains critically unexplored. Artificial endocytosis can be induced by using an amphiphilic molecular machine (AzoMEx) containing a diazocine core (Fig. ), which undergoes an opening-closing motion by photoisomerization to change the distance between two cationic NMe3 + moieties. 66 Interestingly, the light-triggered mechanical motion of AzoMEx embedded in a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)-based giant unilamellar vesicle can expand the liposomal membrane and induce outside-in fission (GUVDOPC/AzoMEx; [DOPC] = 180 µM, [AzoMEx] = 20 µM). This endocytosis-like membrane deformation of GUVDOPC/AzoMEx is useful for the efficient incorporation of large biomacromolecules into the liposomes. GUVDOPC/AzoMEx can interact with 1-µmlong anionic M13 phage virus due to the cationic property of AzoMEx. When the outsidein fission of GUVDOPC/AzoMEx is induced in the presence of M13 phage virus (22.6 × 10 11 virions/mL), M13 phages, as well as AzoMEx, accumulate in the deforming membrane area, and in turn, M13 phages are efficiently incorporated into GUVDOPC/AzoMEx (Fig. ). M13 phages encapsulated into GUVDOPC/AzoMEx were transiently protected from external environments, keeping their infectivity. A fluorescent Cy5-labelled M13 phage (M13 phageCy5) encapsulated in GUVDOPC/AzoMEx whose surface is coated with a block polymer composed of poly(aspartic acid) and poly(ethylene glycol) (GUVDOPC/AzoMEx-pAsp) is administered to mice via the tail vein, and M13 phageCy5 shows higher stability in blood (Fig. and) than bare M13 phageCy5 (Fig. and), as observed by IV-CLSM of the earlobe vessels. After blood administration of M13 phages encapsulated in GUVDOPC/AzoMEx-pAsp, liver, kidney, spleen, lung, heart, and brain were extracted. Importantly, even after distribution to the respective organs through the blood circulation, infectivity of M13 phages was retained (spleen: [25.6 ± 13.2] × 10 9 virions/mg, Fig. ; liver: [18.3 ± 3.2] × 10 9 virions/mg, Fig. ; kidney: [1.3 ± 0.6] × 10 9 virions/mg, Fig. ; heart: [1.1 ± 0.5] × 10 9 virions/mg, Fig. ; lung: [0.5 ± 0.3] × 10 9 virions/mg, Fig. ; and brain: [0.2 ± 0.1] × 10 9 virions/mg, Fig. ). The membrane-expanding molecular machine AzoMEx functionalizes GUV for endocytosis-like fission, which is useful for encapsulation and delivery of biomacromolecules. M13 phages are commonly used in phage display, affinity selection to identify peptides that bind to target molecules. Therefore, the AzoMEx-GUV technology to encapsulate M13 phages for protection from immune cells in the blood could be applied to an in vivo phage display method for selection of peptides that bind to ligands in living bodies.