Organosilica Cages Target Hepatic Sinusoidal Endothelial Cells Avoiding Macrophage Filtering

Abstract

Over the last years, advancements in the use of nanoparticles for biomedical applications have clearly showcased their potential for the preparation of improved imaging and drug-delivery systems. However, compared to the vast number of currently studied nanoparticles for such applications, only a few successfully translate into clinical practice. A common “barrier” that prevents nanoparticles from efficiently delivering their payload to the target site after administration is related to liver filtering, mainly due to nanoparticle uptake by macrophages. This work reports the physicochemical and biological investigation of disulfide-bridged organosilica nanoparticles with cage-like morphology, OSCs, assessing in detail their bioaccumulation in vivo. The fate of intravenously injected 20 nm OSCs was investigated in both healthy and tumor-bearing mice. Interestingly, OSCs exclusively colocalize with hepatic sinusoidal endothelial cells (LSECs) while avoiding Kupffer-cell uptake (less than 6%) under both physiological and pathological conditions. Our findings suggest that organosilica nanocages hold the potential to be used as nanotools for LSECs modulation, potentially impacting key biological processes such as tumor cell extravasation and hepatic immunity to invading metastatic cells or a tolerogenic state in intrahepatic immune cells in autoimmune diseases.

Continuous sensing of IFNα by hepatic endothelial cells shapes a vascular antimetastatic barrier

“…We next took advantage of fluorescence-based techniques to investigate the initial steps of liver colonization. First, we assessed the intrahepatic localization of GFP-expressing MC38 cells (MC38 GFP ) ( Talamini et al, 2021 ) that were intramesenterically challenged 5 min earlier. Most MC38 GFP cells in Ifnar1 fl/fl or VeCad Ifnar1 _KO mice appeared physically trapped at the beginning of the sinusoidal circulation in both mouse lineages.…”

Periodic Mesoporous Ionosilica Nanoparticles for Green Light Photodynamic Therapy and Photochemical Internalization of siRNA

“…In order to enhance the biocompatibility of the nanoparticles, an additional surface functionalization was performed by the subsequent addition of a silylated polyethylene glycol (Silane-PEG 2000). 34 The successful surface modification with PEG groups was monitored via FT-IR spectroscopy (Figure S1). The formation of PMINPs was attested by transmission electron microscopy (TEM).…”

“…The non-ionic surfactant (F127) was used as an inhibitor of grain agglomeration. In order to enhance the biocompatibility of the nanoparticles, an additional surface functionalization was performed by the subsequent addition of a silylated polyethylene glycol (Silane-PEG 2000) . The successful surface modification with PEG groups was monitored via FT-IR spectroscopy (Figure S1).…”

Toxicological impact of titanium dioxide nanoparticles and food-grade titanium dioxide (E171) on human and environmental health

“…58 Liver dysfunction was observed two weeks after a single oral dose of TiO 2 by gavage at 5 mg kg −1 body weight (bw), as indicated by the elevation of circulating transaminases and lactate dehydrogenase, and limited necrosis across the central vein, mainly involving hepatocytes. 59 As reported, systemic treatment with hard nanomaterials often leads to a strong accumulation of NPs in hepatic macrophages 60 or, under particular conditions, in liver sinusoidal cells, 61 whereas the penetration in hepatocytes is rare. This buffer effect, which is crucial to prevent the hepatocyte damage, was abolished by the long-term exposure to TiO 2 NPs (10 mg kg −1 bw TiO 2 NPs for 90 days) that led to Ti accumulation in hepatocyte nuclei, their apoptotic death and a consequent chronic dysfunction.…”