Self-Assembled “Off/On” Nanopomegranate for In Vivo Photoacoustic and Fluorescence Imaging: Strategic Arrangement of Kupffer Cells in Mouse Hepatic Lobules

Abstract

Kupffer cells (KCs), potent scavenger cells located in hepatic sinusoids, constantly phagocytize and degrade foreign materials to maintain metabolism and clearance. Understanding the strategic KC arrangement which links to their spatial location and function in hepatic lobules, the basic functional unit in the liver, is highly valuable for characterizing liver function. However, selectively labeling KCs and characterizing their function in vivo remains challenging. Herein, a fast self-assembled pomegranate structure-like nanoparticle with "nanopomegranate seeds" of dye aggregates has been developed, which has dual-modality "off/on" capability. This nanopomegranate shows good photostability, a high extinction coefficient, a high KC labeling efficiency (98.8%), and better visualization of KC morphology than commercial FluoSpheres. In vivo photoacoustic (PA) and fluorescence imaging consistently visualize that KCs are strategically distributed along the central vein (CV)−portal triad (PT) axis in each liver lobule: more and larger KCs exist in areas closer to the PTs. The high-resolution PA quantitative data further revealed that the density of KCs was linearly dependent on the r n /r max ratio (their relative location along the CV−PT axis) (R 2 = 0.7513), and the KC density at the outermost layer is almost 246-fold that at the innermost layer (each layer is 8 μm). Notably, the phagocytic ability of KCs located in layers with r n /r max ratios of 0.167−0.3 varies in a zigzag pattern, as evidenced by their different PA intensities. Additionally, the fluorescence imaging quantitation suggests similar fluorescence activation of nanopomegranate in KCs. Nanopomegranates combined with dual-modality imaging reveal the strategic arrangement of KCs in vivo, greatly extending our understanding of liver physiology.

Metastatic status of sentinel lymph nodes in breast cancer determined with photoacoustic microscopy via dual-targeting nanoparticles

“…This method has great potential for clinical translation due to combined ultrasound imaging, sPA imaging and MAPS. Previously, we developed a self-assembled nano-pomegranate with the NIR dye DiR-BOA, which has fluorescence/photoacoustic imaging-switching ('off/on') capability 28 . Therefore, we attempted to distinguish the different statuses of LNs using PAM.…”

“…Herein, we developed a novel dual-targeting nanoparticle by inserting the negatively charged HA-1,2-dimyristoyl phosphatidylethanolamine (DMPE) into a single-layer phospholipid of HPPS, denoted HA-HPPS. Importantly, this dual-targeting nanoparticle has a phospholipid monolayer shell containing DiR-BOA, a near-infra-red (NIR) fluorophore, which can be used for both fluorescence imaging and photoacoustic microscopy (PAM) 27 , 28 . We can continuously monitor changes in the DiR-BOA fluorescence signal of LNs in a mouse model (e.g.…”

Nanoparticle delivery in vivo: A fresh look from intravital imaging

“…), Kupffer cells [22] Nano pomegranate-like nanoparticles Organic DiR-BOA Spherical 400 n/a n/a 2 h (i.v. ), Kupffer cells (F4/80 high CD11b int ) [23] Poly(N-(2-hydroxypropyl) methacrylamide) Polymers Organic ATTO 488 and Dy750 Spherical 10 Mannose-decorated n/a Within 2 h (i.v. ), Endothelial cells and Kupffer cells [22] Liposomes Organic Alexa Fluor 750, Alexa Fluor 488 Spherical 100 PEG n/a Within 2 h (i.v.…”

“…Moreover, mannose-decorated polymeric NPs showed higher uptake in endothelial cells as well as by CD206 + Kupffer cells, compared to non-decorated polymeric NPs. In another study, “off/on” NPs with a pomegranate-like structure and a size of ~400 nm were developed to specifically target Kupffer cells [23] . These NPs were used to monitor the spatial distribution of Kupffer cells along the central vein (CV)–portal triad (PT) axis, providing further insights in liver physiology.…”

Toxicity of Zirconia oxide Nanoparticles: Liver Biodistribution and Liver Damages

“…The liver provides the critical function of catabolism and biliary excretion of blood-borne particles, as well as serves as an important site for the elimination of foreign substances and particles [11]. Thus, the liver is a primary target organ in NPs distribution [12,13]. NPs can reach the liver through blood circulation or translocation from the other organs [13][14][15].…”