The Dual Role of the Liver in Nanomedicine as an Actor in the Elimination of Nanostructures or a Therapeutic Target

Abstract

e development of nanostructures for therapeutic purpose is rapidly growing, following the results obtained in vivo in animal models and in the clinical trials. Unfortunately, the potential therapeutic efficacy is not completely exploited, yet. is is mainly due to the fast clearance of the nanostructures in the body. Nanoparticles and the liver have a unique interaction because the liver represents one of the major barriers for drug delivery. is interaction becomes even more relevant and complex when the drug delivery strategies employing nanostructures are proposed for the therapy of liver diseases, such as hepatocellular carcinoma (HCC). In this case, the selective delivery of therapeutic nanoparticles to the tumor microenvironment collides with the tendency of nanostructures to be quickly eliminated by the organ. e design of a new therapeutic approach based on nanoparticles to treat HCC has to particularly take into consideration passive and active mechanisms to avoid or delay liver elimination and to specifically address cancer cells or the cancer microenvironment. is review will analyze the different aspects concerning the dual role of the liver, both as an organ carrying out a clearance activity for the nanostructures and as target for therapeutic strategies for HCC treatment.

Glutathione-responsive cyclodextrin-nanosponges as drug delivery systems for doxorubicin: Evaluation of toxicity and transport mechanisms in the liver

“…Thus, in the present study our attention focused on hepatotoxicity for two main reasons: on the one hand it is well-known that Dox can cause liver toxicity (Bagchi et al1995); furthermore, it has been shown that this organ, being one of the main filters of the human body, can capture the exogenous nanoparticles in the circulation, leading to toxicity (Zhang et al 2016). Reasons for liver accumulation of NPs may include the sheer size of the liver (Bartneck et al 2014), its highly fenestrated endothelium (Abdel-Misih and Bloomston 2010), as well as the high number of Kupffer cells, the resident macrophages in the liver (Baboci et al 2020, Kretzschmar 1996.…”

MicroRNA Therapeutics in Cancer: Current Advances and Challenges

“…Plasma levels of synthetic miRNA antagonists or miRNA mimics distribute broadly after intravenous administration but later accumulate mostly in the liver and kidney and remain high up to 24 h after injection [ 118 ]. On the other hand, NPs biodistribution studies have demonstrated that the majority of injected nanomaterials usually accumulate in the liver before undergoing hepatic clearance [ 119 ]. This makes liver cancer a good model for testing miRNA-based therapy approaches as this organ can be easily targeted with different delivery systems.…”

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