Fig. 3: Mechanism exploration for intercellular transport of sLip/Dox in liver.

a Diagram of sLip/Dox interaction with various liver cells. The sLip with different particle sizes (90, 120, or 300 nm) encapsuled Dox distribution in KC (b) and LSEC (c, d) at 4 or 12 h post injection with KC depletion or not. e Distribution of sLip/Dox (90 nm) in zonated HC at 4 h post injection with KC depletion or not. f Distribution of sLip/Dox (90, 120, or 300 nm) in zonated HC at 4 h post injection with KC depletion. g Distribution of sLip/Dox (90, 120, or 300 nm) in zonated HC at 4 h post injection in KC-normal condition. The sLip/Dox was intravenously injected at a dose of 5 mg/kg doxorubicin. The statistical significance was analyzed by one-way ANOVA multiple comparisons corrected by Tukey’s test for (b, f, g), and by two-way ANOVA multiple comparisons corrected by Sidak’s test for (c–e). P values are provided when there are statistical significances (P < 0.05). Data were means ± SDs for (b–g) (n = 3 mice). h Rough calculation of total Dox distribution in major liver cells at 4 h after injection. The %liver cells ratio referred to ref. ¹⁸, as 6% for KC, 15% for LSEC, and 23.3% for cHC, mHC, pHC, respectively, considering a total HC occupied about 70% of the total liver cells. i The schematic of intercellular transport pathway for sLip/Dox in liver. For intravenously injected sLip/Dox, firstly KC captured the liposomes and resulted in intracellular degradation, then Dox released extracellularly and transported across liver sinusoid endothelial fenestration into HC, and zonally accumulated in HC along the lobule porto-central axis. LSEC capture for sLip/Dox was less than that in KC and probably shielded by KC. j Regulatory effects of particle sizes variation or KC function on HC accumulation of Dox encapsuled in PEGylated liposomes. Source data are provided as a Source Data file.