Scheme 1

Schematic of the PFCnD-based intracerebral delivery strategy. (A) Schematic illustration of the two PFCnDs species for BBB opening and contrast-enhanced US/PA imaging. The core materials were optimized for specific functions with PFH used for BBB opening and PFP used for CEUS imaging. The two nanodroplets species were loaded with optical dyes having peak optical absorbances of 1064 nm (PFCnDs-1064) and 760 nm (PFCnDs-760), enabling multiplex PA imaging and independent activation. Both species were synthesized with a lipid shell. (B) Schematic diagram of the experimental intracerebral delivery protocol. (B-1) Mice received a retro-orbital injection of PFCnDs-1064. (B-2) Mice received external laser stimulation at a wavelength of 1064 nm through the skull on the right side of the head. (B-3) Mice received an intra-jugular injection of PFCnDs-760. (C) Schematic diagram of the intracerebral delivery approach mechanism. (C-1) Intravenously injected PFCnDs-1064 flow into cerebral microvessels and approach the BBB. (C-2) Laser-stimulation induces PFCnDs-1064 cavitation and local BBB opening. (C-3) Intravenously injected PFCnDs enter brain tissue through the opened BBB