Explore chapters and articles related to this topic
Breast Imaging with Radiolabeled Peptides
Published in Raymond Taillefer, Iraj Khalkhali, Alan D. Waxman, Hans J. Biersack, Radionuclide Imaging of the Breast, 2021
Eric P. Krenning, Marion de Jong, Roelf Valkema, Casper H.J. van Eijck
In general, receptor-mediated endocytosis systems have been described [58,59], where cell surface receptors capture their ligands from the extracellular milieu. The receptor-ligand complex is internalized via invagination of the plasma membrane. The resulting intracellular vesicles, termed endosomes, rapidly acidify, which causes the ligand to dissociate from the receptor. The ligand is delivered to the lysosome [60], and the receptor may recycle back to plasma membrane. The whole process takes approximately 15 min [58], and a single receptor can deliver numerous ligand molecules to the lysosomes. We have studied internalization and degradation of radiolabeled [DTPA°]octreotide in the somatostatin receptor-positive rat pancreatic tumor cell lines CA20948 and AR42J and in the somatostatin receptor-negative human anaplastic thyroid tumor cell line ARO and detected internalization of the radiopharmaceutical in vitro, in accordance with the findings of Andersson et al. [61], and found that this process was receptor-specific and temperature-dependent [62], Earlier, we reported in vitro studies using AtT20 mouse pituitary tumor cells for detection of internalization of [125I-Tyr3]octreotide [63],
Structural Organization of the Liver
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
The macromolecules internalized by receptor-mediated endocytosis include serum proteins, such as low-density lipoprotein (LDL); asialoglyco-proteins and transferin; hormones, such as insulin and epidermal growth factor (EGF); immunoglobulin A; and lysosomal enzymes. In addition to those substances normally taken up by cells, certain infectious agents such as many enveloped viruses and toxins seem to enter the cell through a receptor-mediated process (Forgac, 1988). Since proteins can be fixed and retained in the cell for morphological examination and their identity in situ can be confirmed immunologically and/or autoradiographically, or biochemically in isolated subcellular fractions, considerable progress has been made during the past decade in understanding the structure-function correlation of receptor-mediated endocytosis and related intracellular vesicular transport.
Imaging of Intracellular Targets
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Large and hydrophilic molecules can enter the cell through different types of endocytosis, a process by which cells absorb molecules by invagination of the plasma membrane. Substances may be taken up by endocytosis after binding to a receptor, by interacting with other structures on the cell surface, or just by being engulfed together with fluid surrounding the cell when an endocytic vesicle is formed. There are multiple types of endocytic pathways of which the clathrin-mediated endocytosis pathway is best known and by far the best studied. Additionally, several clathrin-independent endocytosis mechanisms have been described (Sandvig et al. 2008; Howes et al. 2010; Kumari et al. 2010), including dynamin-dependent mechanisms and dynamin-independent mechanisms. It should be noted that receptor-mediated endocytosis can involve several of the aforementioned mechanisms, dependent on the type of receptor being used.
Zinc pyrithione is a potent inhibitor of PLPro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Jerneja Kladnik, Ana Dolinar, Jakob Kljun, David Perea, Judith Grau-Expósito, Meritxell Genescà, Marko Novinec, Maria J. Buzon, Iztok Turel
Research and development of safe and effective pharmacotherapy for a life-threatening COVID-19 disease must now focus on curative approaches after the rapid and successful development of SARS-CoV-2 vaccines. The development of specific SARS-CoV-2 inhibitors requires a thorough knowledge of viral structure, host cell entry, and the replication cycle1. SARS-CoV-2 is an enveloped single-stranded positive-sense RNA virus2 that requires binding of the viral spike protein to the human zinc metalloproteinase receptor ACE2 as the first step in internalisation process3. After binding, viral entry is possible through (i) direct fusion with the cell surface involving the proteases furin and transmembrane serine protease-2 (TMPRSS2), followed by direct release of SARS-CoV-2 RNA and/or (ii) receptor-mediated endocytosis, in which the lysosomal cysteine protease cathepsin L facilitates the release of the genetic material after fusion of the viral and endosomal membranes4. Once RNA is released into the cytosol, translation and replication of the genome occur, including the potential targets papain-like protease (PLPro), chymotrypsin-like protease (3CLPro, also abbreviated as MPro), and RNA-dependent RNA polymerase (RdRp). After the synthesis of the viral structural proteins and their transition through endoplasmatic-reticulum-to-Golgi intermediate compartment, the viral copies are released from host cells by exocytosis5.
Avelumab internalization by human circulating immune cells is mediated by both Fc gamma receptor and PD-L1 binding
Published in OncoImmunology, 2021
Hulin Jin, Vittorio D'Urso, Berend Neuteboom, Sean D. McKenna, Rene Schweickhardt, Alec W. Gross, Yves Fomekong Nanfack, Andrea Paoletti, Carina Carter, Lars Toleikis, Markus Fluck, Juergen Scheuenpflug, Ti Cai
All approved monoclonal antibodies developed to date are IgG, and their elimination from the body mostly occurs via intracellular catabolism after nonspecific fluid-phase pinocytosis or receptor-mediated endocytosis.8 Following the binding of the antibody Fab region to cell surface proteins, receptor-mediated endocytosis results in antibody recycling via endosomes or degradation within lysosomes. Thus, target binding can significantly contribute to the kinetics of antibody elimination. IgG antibodies can also trigger elimination through binding of their Fc region to Fcγ receptors (FcγRs).8 These receptors are expressed on various types of immune cells that can be recruited to tumors through FcγR-Fc interactions with antibody-bound targets.9 Recruited immune cells can then elicit or mediate immunologic activities, including endocytosis and phagocytosis.8,9 FcγR-mediated elimination might dominate when an antibody can form soluble immune complexes with three or more IgGs, or in cases where the antibody binds cells suspended in blood or body fluid.8
Stimuli-responsive drug delivery systems for head and neck cancer therapy
Published in Drug Delivery, 2021
Jingou Liang, Bina Yang, Xuedong Zhou, Qi Han, Jing Zou, Lei Cheng
Furthermore, the stimuli-responsive DDSs could also be modified, yielding multifunctional DDSs, for active drug delivery, integration of diagnosis and treatment, combined therapy and so on. For instance, for enhanced delivery efficient and specificity, increasing number of researchers developed DDSs with active targeting properties rather than that with EPR effect. Ligand/receptor-mediated endocytosis is among the most used strategies. The DDSs carriers could be linked with various kinds of ligands which could recognize specific receptors on tumor cells, thus leading to improved internalization to tumor cells and cell killing effect (Liu, Gao, et al., 2014; Li, Wen, You, et al., 2016; Nam et al., 2018). Some magnet-based DDSs or DDSs co-loading with fluorescent materials have been designed for theranostic applications which could combine cancer imaging with treatment (Kim et al., 2013; Bhana et al., 2015; Haedicke et al., 2015). Besides, co-delivery of antitumor agents such as chemotherapeutic drugs, photosensitizers (PSs) and gene materials could demonstrate synergistic therapeutic effect and reduced side effect, which showed great research potential recently (Ma, 2014; Miao et al., 2014; Wang et al., 2016).