Fig. 9

AM-NPs accelerate clearance of fAβ. a–d Electron microscope micrographs of BV2 microglia incubated with NPs for 24 h, then co-incubated with fAβ for 30 min. Cells were fixed with a mixture of 2.5% glutaraldehyde and 4% PFA in 0.1 M cacodylate buffer at pH 7.4. Ultrathin (90 nm) sections of cell pellets were imaged using the electron microscope. a, e The ultrastructure of a microglia treated with fAβ only. The intracellular fAβ (white arrowhead) is surrounded by damaged vacuoles, including large autophagosomes (white arrows) and lysosomes with incomplete membranes (yellow arrows). Mitochondria (M) in this cell is structurally damaged, as evidenced by disordered cristae and a thin outer membrane (e). b, f The ultrastructure of a fAβ-treated microglia co-incubated with T₁₂P₅(PS). In this cell, the phagocytic activity is high, as illustrated by the high representation of a variety of autophagosomes (white arrows), lysosomes with well-developed membranes (yellow arrows), and autophagosome-lysosome fusion structures (blue arrows). Mitochondria in this cell are intact, as evidenced by well-defined cristae structures and an intact outer membrane (f). c, g The ultrastructure of fAβ-treated microglia co-incubated with M₁₂P₅(PS). The phagocytic activity is less, as illustrated by fewer autophagosomes (white arrows); however, the lysosomal structures are characterized by a well-developed double membrane (yellow arrows). This cell has a high representation of intact and long mitochondria characterized by well-defined cristae and an intact outer membrane (g). d, h The ultrastructure of fAβ-treated microglia co-incubated with the control PS-b-PEG(PS). A large center of fAβ is present in this cell, along with large thin-walled autophagosomes (white arrows) and thin-walled lysosomal structures (yellow arrows). Mitochondria in this cell are structurally damaged, as evidenced by distorted cristae and thin outer membrane. N, nucleus, and M, mitochondria. Scale bars, 500 nm in the top panels of a–d and e–h; 1 µm in the bottom panels in a–d