Fig. 6: A scheme diagram of intrahepatic cellular interaction of sLip/Dox from blood circulation and following excretion.

a The whole journey of sLip/Dox suffering hepatobiliary elimination. Intravenously injected sLip/Dox is stable in blood circulation and maintains intact to reach liver sinusoid, where sLip/Dox is mainly captured by KC and LSEC. KC tends to display fast and high endocytosis of sLip/Dox to cause the degradation of liposomes and Dox release to extracellular sites. LSEC uptake of sLip/Dox seems to be shielded by KC and captures sLip/Dox in a slow and moderate manner after KC saturation. Dox accumulation and metabolism in HC is supplied from KC/LSEC in a free form, and displays a zonated distribution from cHC to pHC, subsequently Dox and the metabolites (mainly Doxol) constantly infuse into the gall bladder. Dox secreted into the intestine mainly suffers metabolizing to 7-Deo, and would be a limited reabsorption due to P-glycoprotein, eventually out of the body in feces. b sLip/Dox infusion in liver sinusoid would be directly captured by KC (a), LSEC (b), and transferred into HC (c), subsequently suffering bile secretion.