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WIREs Nanomed Nanobiotechnol
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Critical considerations for targeting colorectal liver metastases with nanotechnology

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Abstract Colorectal cancer remains a significant cause of morbidity and mortality worldwide. Half of all patients develop liver metastases, presenting unique challenges for their treatment. The shortcomings of conventional chemotherapy has encouraged the use of nanomedicines; the application of nanotechnology in the diagnosis and treatment of disease. In spite of technological improvements in nanotechnology, the complexity of biological systems hinders the prospect of nanomedicines being applied in cancer therapy at the present time. This review highlights current biological barriers and discusses aspects of tumor biology together with the physicochemical features of the nanocarrier, that need to be considered in order to develop effective nanotherapeutics for colorectal cancer patients with liver metastases. It becomes clear that incorporating an interdisciplinary approach when developing nanomedicines should assure appropriate disease‐driven design and that this will form a critical step in improving their clinical translation. This article is characterized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Schematic overview of a liver lobule highlighting the different hepatic cells. Oxygenated blood from terminal branches of the portal vein and hepatic artery merge upon entry into the liver sinusoids and drains into the central vein. The sinusoids are surrounded by fenestrated liver sinusoidal endothelial cells, which form a discontinuous endothelium that allows for bidirectional metabolic exchange. Kupffer cells, the specialized macrophages of the liver, are located in the lumen of the sinusoids and their primary function involves the removal of particulates from the portal blood. Hepatic stellate cells are positioned in the space of Disse and play a key role in the production of growth factors and cytokines. Hepatocytes, the functional unit of the liver, are arranged as interconnecting sheets of cells that surround the sinusoids. Bile produced by hepatocytes is collected into the bile ducts via the bile canaliculi. Cholangiocytes are the epithelial cells found lining the bile ducts
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Overview of several key interactions involving nanoparticles within the tumor
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Schematic representation of passive and actively targeted nanoparticle (NP) delivery systems. By taking advantage of the enhanced permeability and retention (EPR) effect, nontargeted NPs are able to passively extravasate through the leaky vasculature and accumulate within the tumor (upper). Alternatively, the surface of NPs can be conjugated with targeting moieties to actively bind with a cell‐specific target (lower). This allows for enhanced cellular uptake inside the tumor
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Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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