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      Overcoming Ovarian Cancer Drug Resistance with a Cold Responsive Nanomaterial

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          Abstract

          Drug resistance due to overexpression of membrane transporters in cancer cells and the existence of cancer stem cells (CSCs) is a major hurdle to effective and safe cancer chemotherapy. Nanoparticles have been explored to overcome cancer drug resistance. However, drug slowly released from nanoparticles can still be efficiently pumped out of drug-resistant cells. Here, a hybrid nanoparticle of phospholipid and polymers is developed to achieve cold-triggered burst release of encapsulated drug. With ice cooling to below ∼12 °C for both burst drug release and reduced membrane transporter activity, binding of the drug with its target in drug-resistant cells is evident, while it is minimal in the cells kept at 37 °C. Moreover, targeted drug delivery with the cold-responsive nanoparticles in combination with ice cooling not only can effectively kill drug-resistant ovarian cancer cells and their CSCs in vitro but also destroy both subcutaneous and orthotopic ovarian tumors in vivo with no evident systemic toxicity.

          Abstract

          A cold-responsive hybrid nanoparticle of phospholipid and polymers is developed to overcome the multidrug resistance of cancer stem cells with ice cooling.

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          Drug resistance and the solid tumor microenvironment.

          Olivier Trédan, Carlos M. Galmarini, Krupa Patel … (2007)
          Resistance of human tumors to anticancer drugs is most often ascribed to gene mutations, gene amplification, or epigenetic changes that influence the uptake, metabolism, or export of drugs from single cells. Another important yet little-appreciated cause of anticancer drug resistance is the limited ability of drugs to penetrate tumor tissue and to reach all of the tumor cells in a potentially lethal concentration. To reach all viable cells in the tumor, anticancer drugs must be delivered efficiently through the tumor vasculature, cross the vessel wall, and traverse the tumor tissue. In addition, heterogeneity within the tumor microenvironment leads to marked gradients in the rate of cell proliferation and to regions of hypoxia and acidity, all of which can influence the sensitivity of the tumor cells to drug treatment. In this review, we describe how the tumor microenvironment may be involved in the resistance of solid tumors to chemotherapy and discuss potential strategies to improve the effectiveness of drug treatment by modifying factors relating to the tumor microenvironment.
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            Tumor-selective catalytic nanomedicine by nanocatalyst delivery

            Minfeng Huo, Liying Wang, Yu Chen … (2017)
            Tumor cells metabolize in distinct pathways compared with most normal tissue cells. The resulting tumor microenvironment would provide characteristic physiochemical conditions for selective tumor modalities. Here we introduce a concept of sequential catalytic nanomedicine for efficient tumor therapy by designing and delivering biocompatible nanocatalysts into tumor sites. Natural glucose oxidase (GOD, enzyme catalyst) and ultrasmall Fe3O4 nanoparticles (inorganic nanozyme, Fenton reaction catalyst) have been integrated into the large pore-sized and biodegradable dendritic silica nanoparticles to fabricate the sequential nanocatalyst. GOD in sequential nanocatalyst could effectively deplete glucose in tumor cells, and meanwhile produce a considerable amount of H2O2 for subsequent Fenton-like reaction catalyzed by Fe3O4 nanoparticles in response to mild acidic tumor microenvironment. Highly toxic hydroxyl radicals are generated through these sequential catalytic reactions to trigger the apoptosis and death of tumor cells. The current work manifests a proof of concept of catalytic nanomedicine by approaching selectivity and efficiency concurrently for tumor therapeutics.
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              Endocytosis and exocytosis of nanoparticles in mammalian cells

              Nuri Oh, Ji-Ho Park (2014)
              Engineered nanoparticles that can be injected into the human body hold tremendous potential to detect and treat complex diseases. Understanding of the endocytosis and exocytosis mechanisms of nanoparticles is essential for safe and efficient therapeutic application. In particular, exocytosis is of significance in the removal of nanoparticles with drugs and contrast agents from the body, while endocytosis is of great importance for the targeting of nanoparticles in disease sites. Here, we review the recent research on the endocytosis and exocytosis of functionalized nanoparticles based on various sizes, shapes, and surface chemistries. We believe that this review contributes to the design of safe nanoparticles that can efficiently enter and leave human cells and tissues.
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                Author and article information

                Journal
                Journal ID (nlm-ta): ACS Cent Sci
                Journal ID (iso-abbrev): ACS Cent Sci
                Journal ID (publisher-id): oc
                Journal ID (coden): acscii
                Title: ACS Central Science
                Publisher: American Chemical Society
                ISSN (Print): 2374-7943
                ISSN (Electronic): 2374-7951
                Publication date (Electronic): 17 April 2018
                Publication date (Print): 23 May 2018
                Volume: 4
                Issue: 5
                Pages: 567-581
                Affiliations
                [11] †Fischell Department of Bioengineering and #Robert E. Fischell Institute for Biomedical Devices, University of Maryland , College Park, Maryland 20742, United States
                [22] ‡Department of Biomedical Engineering and §Comprehensive Cancer Center, The Ohio State University , Columbus, Ohio 43210, United States
                [∥ ]Center for Biomedical Engineering, Department of Electronic Science and Technology, University of Science and Technology of China , Hefei, Anhui 230027, China
                [⊥ ]Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai 200032, China
                [∇ ]Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland , Baltimore, Maryland 21201, United States
                [○ ]Department of Microbiology and Immunology, University of Maryland School of Medicine , Baltimore, Maryland 21201, United States
                [◆ ]United States Department of Veterans Affairs, Maryland VA Health Care System , Baltimore, Maryland 21201, United States
                [● ]Department of Medical and Molecular Genetics and Melvin and Bren Simon Cancer Center, Indiana University School of Medicine , Indianapolis, Indiana 46202, United States
                Author notes
                Article
                DOI: 10.1021/acscentsci.8b00050
                PMC ID: 5968444
                PubMed ID: 29806003
                SO-VID: c3e0df19-a5d1-4c77-9f38-bde24075617f
                Copyright © Copyright © 2018 American Chemical Society
                License:

                This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

                History
                Date received : 18 January 2018
                Categories
                Subject: Research Article
                Custom metadata
                document-id-old-9 oc8b00050
                document-id-new-14 oc-2018-00050h
                ccc-price

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