6
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Intracellular trafficking of new anticancer therapeutics: antibody–drug conjugates

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Antibody–drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs.

          Related collections

          Most cited references 97

          • Record: found
          • Abstract: found
          • Article: not found

          Regulated portals of entry into the cell.

          The plasma membrane is the interface between cells and their harsh environment. Uptake of nutrients and all communication among cells and between cells and their environment occurs through this interface. 'Endocytosis' encompasses several diverse mechanisms by which cells internalize macromolecules and particles into transport vesicles derived from the plasma membrane. It controls entry into the cell and has a crucial role in development, the immune response, neurotransmission, intercellular communication, signal transduction, and cellular and organismal homeostasis. As the complexity of molecular interactions governing endocytosis are revealed, it has become increasingly clear that it is tightly coordinated and coupled with overall cell physiology and thus, must be viewed in a broader context than simple vesicular trafficking.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The multiple faces of caveolae.

            Caveolae are a highly abundant but enigmatic feature of mammalian cells. They form remarkably stable membrane domains at the plasma membrane but can also function as carriers in the exocytic and endocytic pathways. The apparently diverse functions of caveolae, including mechanosensing and lipid regulation, might be linked to their ability to respond to plasma membrane changes, a property that is dependent on their specialized lipid composition and biophysical properties.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Virus entry by macropinocytosis.

              As obligatory intracellular parasites, viruses rely on host-cell functions for most aspects of their replication cycle. This is born out during entry, when most viruses that infect vertebrate and insect cells exploit the endocytic activities of the host cell to move into the cytoplasm. Viruses belonging to vaccinia, adeno, picorna and other virus families have been reported to take advantage of macropinocytosis, an endocytic mechanism normally involved in fluid uptake. The virus particles first activate signalling pathways that trigger actin-mediated membrane ruffling and blebbing. Usually, this is followed by the formation of large vacuoles (macropinosomes) at the plasma membrane, internalization of virus particles and penetration by the viruses or their capsids into the cytosol through the limiting membrane of the macropinosomes. We review the molecular machinery involved in macropinocytosis and describe what is known about its role in virus entry.
                Bookmark

                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2017
                02 August 2017
                : 11
                : 2265-2276
                Affiliations
                [1 ]Department of Biochemistry and Genetics, School of Medicine
                [2 ]Department of Pharmaceutical Analysis, College of Pharmaceutical Science, Zhejiang University, Hangzhou, People’s Republic of China
                Author notes
                Correspondence: Jinbiao Zhan, Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, People’s Republic of China, Tel +86 571 8820 8272, Fax +86 571 8820 8273, Email jzhan2k@ 123456zju.edu.cn
                Article
                dddt-11-2265
                10.2147/DDDT.S135571
                5546728
                © 2017 Kalim et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Review

                Comments

                Comment on this article