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      How can we use the endocytosis pathways to design nanoparticle drug-delivery vehicles to target cancer cells over healthy cells?

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          Abstract

          Targeted drug delivery in cancer typically focuses on maximising the endocytosis of drugs into the diseased cells.

          Abstract

          Targeted drug delivery in cancer typically focuses on maximising the endocytosis of drugs into the diseased cells. However, there has been less focus on exploiting the differences in the endocytosis pathways of cancer cells versus non-cancer cells. An understanding of the endocytosis pathways in both cancer and non-cancer cells allows for the design of nanoparticles to deliver drugs to cancer cells whilst restricting healthy cells from taking up anticancer drugs, thus efficiently killing the cancer cells. Herein we compare the differences in the endocytosis pathways of cancer and healthy cells. Second, we highlight the importance of the physicochemical properties of nanoparticles (size, shape, stiffness, and surface chemistry) on cellular uptake and how they can be adjusted to selectively target the dominated endocytosis pathway of cancer cells over healthy cells and to deliver anticancer drug to the target cells. The review generates new thought in the design of cancer-selective nanoparticles based on the endocytosis pathways.

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          The Emerging Hallmarks of Cancer Metabolism.

          Tumorigenesis is dependent on the reprogramming of cellular metabolism as both direct and indirect consequence of oncogenic mutations. A common feature of cancer cell metabolism is the ability to acquire necessary nutrients from a frequently nutrient-poor environment and utilize these nutrients to both maintain viability and build new biomass. The alterations in intracellular and extracellular metabolites that can accompany cancer-associated metabolic reprogramming have profound effects on gene expression, cellular differentiation, and the tumor microenvironment. In this Perspective, we have organized known cancer-associated metabolic changes into six hallmarks: (1) deregulated uptake of glucose and amino acids, (2) use of opportunistic modes of nutrient acquisition, (3) use of glycolysis/TCA cycle intermediates for biosynthesis and NADPH production, (4) increased demand for nitrogen, (5) alterations in metabolite-driven gene regulation, and (6) metabolic interactions with the microenvironment. While few tumors display all six hallmarks, most display several. The specific hallmarks exhibited by an individual tumor may ultimately contribute to better tumor classification and aid in directing treatment.
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            Cellular uptake of nanoparticles: journey inside the cell

            Cellular association and trafficking of nanoscale materials enables us to both understand and exploit context-dependent phenomena in various disease states, their pathogenesis, and potential therapeutic approaches. Nanoscale materials are increasingly found in consumer goods, electronics, and pharmaceuticals. While these particles interact with the body in myriad ways, their beneficial and/or deleterious effects ultimately arise from interactions at the cellular and subcellular level. Nanoparticles (NPs) can modulate cell fate, induce or prevent mutations, initiate cell–cell communication, and modulate cell structure in a manner dictated largely by phenomena at the nano–bio interface. Recent advances in chemical synthesis have yielded new nanoscale materials with precisely defined biochemical features, and emerging analytical techniques have shed light on nuanced and context-dependent nano-bio interactions within cells. In this review, we provide an objective and comprehensive account of our current understanding of the cellular uptake of NPs and the underlying parameters controlling the nano-cellular interactions, along with the available analytical techniques to follow and track these processes.
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              Macrophages and Metabolism in the Tumor Microenvironment

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                Author and article information

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                Journal
                CSRVBR
                Chemical Society Reviews
                Chem. Soc. Rev.
                Royal Society of Chemistry (RSC)
                0306-0012
                1460-4744
                August 30 2022
                2022
                : 51
                : 17
                : 7531-7559
                Affiliations
                [1 ]School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia
                [2 ]Australian Centre for NanoMedicine, University of New South Wales, Sydney, NSW 2052, Australia
                [3 ]Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2052, Australia
                [4 ]School of Clinical Medicine, UNSW Medicine & Health, University of New South Wales, Sydney, NSW 2052, Australia
                [5 ]School of Chemical Engineering and Technology, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, Xi’an Jiao Tong University, Xi’an, China
                Article
                10.1039/D1CS00707F
                35938511
                cb1e2ef8-0fe1-447a-a48f-c21f156c28f4
                © 2022

                http://rsc.li/journals-terms-of-use

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