Fig. 1
Transferrin-functionalized nanoparticles cross the intact BBB. a Schematic of a PEGylated dual drug-loading liposome that can be functionalized to enhance transport across the BBB and targeting to glioma cells. b Cranial window (black oval delineating region of craniotomy) exposing the brain for in vivo multiphoton imaging. Multiphoton images of: c A brain microvessel showing lack of transport of Hemagglutinin-PEG2K-Cy5.5 liposomes across the BBB; d Diffusion of transferrin-PEG2K-Cy5.5 (Tf-NP) liposomes across the endothelium of a brain microvessel (outlined in white) with nanoparticle aggregates in the subarachnoid space (white arrows); and e Composite image showing accumulation of Tf-NP liposomes in the endothelial wall of a brain microvessel (white arrows) with diffusion across the BBB and aggregation of liposomal nanoparticles in the surrounding brain milieu. White outline depicts bony edge of the cranial window with bone second harmonic signal in blue. Images were taken 24 h following a single tail vein injection of nanoparticles. All scale bars = 25 μm
