In vivo (A) and ex vivo (B) images of BSA NP, BSA MP, and BSA MTN in infected mouse models assessed by live imaging. Mice used in experiments were infected with C. neoformans for 48 h and then tail-vein injected with DiR-loaded preparations. Ex vivo images of various tissues from infected mice were collected after mice were euthanized 8 h after injection. (C) In vivo distribution of BSA NP/AmB, BSA MP/AmB, and BSA MTN/AmB in the brain, heart, lungs, liver, spleen, and kidneys of infected mice at different time points. Data are presented as mean ± SD (n = 3). ∗P < 0.05, ∗∗P < 0.01. (D) MMP-3 protein expression in the lungs of normal and infected mice determined by immunofluorescence. C. neoformans were labeled with RFP and shown as red, pulmonary tissues were labeled with MMP-3 (green) (scale bar = 20 μm). (E) Immunofluorescence of the colocalization of SPARC and comarin-6-labeled NPs in infected mice (Scale bar = 20 μm). (F) Fluorescence imaging was used to observe the intracellular interaction between BSA NP and normal/infected cells in vivo. RFP-tagged C. neoformans was used for intracellular infection. NPs were labeled with coumarin-6 (scale bar = 5 μm).