Nanomaterial Manipulation of Immune Microenvironment in the Diseased Liver

Abstract

The liver contains intricate immunological mechanisms, capable of inducing both immune activation and suppression for the maintenance of a homeostatic immune environment. From an immunological point of view, chronic liver disease is indeed a result of the imbalance of pro-and anti-inflammatory responses. Therefore, application of immunotherapy in liver diseases is logical and contains a huge potential for future development. Despite rapid advances in immunotherapy, research at the interdisciplinary interface of immunology and material science is important for further enhancement of immunotherapeutic efficiency and reduction of side effects. Moreover, the liver is particularly suitable for the application of nanomaterial-based immunotherapy due to its biological filtration function to sequester a majority of administrated nanoparticles from systemic circulation. Here, an insight of advanced liver diseases and how liver cells exert their immune functions in the diseased liver is summarized first to provide basic principles for therapeutic application, followed by an overview of the latest studies on nanomaterial-based immunotherapy for liver diseases.

RNA nanotherapeutics for hepatocellular carcinoma treatment

“…Given the liver's filtering capacity and complex microenvironment, designing RNA nanomedicines requires specific adaptations to enhance delivery efficiency. For instance, leveraging the high endocytic activity of LSECs can enhance the efficiency of RNA delivery systems, and specific cellular interactions within the liver microenvironment can be exploited to improve the uptake and efficacy of therapeutic RNA 100 . Recent studies have shown that after entering the liver, PEGylated liposomal drugs are first taken up by Kupffer cells, where the liposomes are degraded intracellularly, releasing free drugs that evade LSEC capture and directly enter hepatocytes 101 .…”

Novel Trends in Revolutionizing Hepatic Diseases Treatment: Application of Nanotechnology..

“…To determine whether nanoparticles have superior cell or tissue targeting capacity, there are fundamental factors such as size, surface charge, and hydrophilic properties. The adjustments of physicochemical features in nano medicine enable it to reach and enter liver cells in a passivetargeted manner, which leads to an increase in the accumulation of the liver, reducing renal clearance and unwanted distribution in other organs (74).…”

“…The low plaque accumulation is due to rapidly cleared nanoparticles by renal filtration, which is smaller than 5 nm. The forced extrusion is used in diffusing nanoparticles with diameters > 400 nm through the sinusoid endothelial fenestrations ,supposing due to transient interaction with the sinusoidal endothelial cells (74,75). So, by Kupffer cells, the particles with larger sizes ,especially 200-1000 nm, are more likely to be phagocytized.…”

“…After administration of nanoparticles in blood, The protein corona is formed due to non-specific interactions between serum proteins and nanoparticles, which mediates the uptake of non-targeted nanoparticles into hepatic cells (74) .…”

Applications of Nanobiomaterials in the Therapy and Imaging of Acute Liver Failure

“…The specific properties of nanoparticles such as size, hydrophilicity, and surface charge are the most fundamental factors that determine whether they have superior cell or tissue targeting capacity. Appropriate adjustments of the physicochemical features enable nanomedicines to enter liver cells in a passive-targeted manner, thereby increasing the accumulation of liver and reducing renal clearance and undesired distribution in other organs [24]. Particle size notably affects cell and tissue uptake.…”