Abstract
Background: Achieving efficient extravascular nanoparticle delivery to deep viscera is hindered by rapid reticuloendothelial clearance and multiple biological barriers. We explored whether the linea alba (LA) interstitium acts as a route for gold nanoparticle (AuNP) delivery. Methods: PEGylated 20 nm AuNPs were interstitially injected into the rat LA under anesthetized, awake, electroacupuncture (EA), and moxibustion (Moxi) conditions; paramedian muscle and tail vein injections served as controls. Results: Micro-CT and ICP-MS showed that LA injection supported directional AuNP migration along the midline, with relatively high normalized concentration-based index values for the ovaries (23.04%) and bladder (20.22%). By comparison, intravenous injection was associated with higher normalized values in the liver, spleen, and lungs. The awake state promoted systemic entry of Au and splenic accumulation; EA increased Au distribution within the uterus; and Moxi boosted systemic transport. Histology identified a loose reticular collagen network with expanded interstitial spaces within the LA. Conclusions: These findings suggest that the LA interstitium is a promising interstitial nano-delivery pathway, where nanoparticle biodistribution can be tuned by physiological status and physical stimuli.