scholarly journals A comparative analysis of cell surface targeting aptamers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Linsley Kelly ◽  
Keith E. Maier ◽  
Amy Yan ◽  
Matthew Levy
Keyword(s):  
Cell Surface ◽  
Near Infrared ◽  
Targeted Therapeutics ◽  
Sirna Transfection ◽  
Binding Properties ◽  
Surface Receptors ◽  
Prostate Cancers ◽  
And Function ◽  
Assay Conditions

AbstractAptamers represent a potentially important class of ligands for the development of diagnostics and therapeutics. However, it is often difficult to compare the function and specificity of many of these molecules as assay formats and conditions vary greatly. Here, with an interest in developing aptamer targeted therapeutics that could effectively deliver cargoes to cells, we chemically synthesize 15 aptamers that have been reported to target cell surface receptors or cells. Using standardized assay conditions, we assess each aptamer’s binding properties on a panel of 11 different cancer cell lines, correlate aptamer binding to antibody controls and use siRNA transfection to validate each aptamer’s binding to reported target receptors. Using a subset of these molecules known to be expressed on prostate cancers, we use near-infrared in vivo imaging to assess the tumor localization following intravenous injection. Our data demonstrate some surprising differences in the reported specificity and function for many of these molecules and raise concerns regarding their cell targeting capabilities. They also identify an anti-human transferrin aptamer, Waz, as a robust candidate for targeting prostate cancers and for future development of aptamer-based therapeutics.

scholarly journals Oligo-guanosine nucleotide induces neuropilin-1 internalization in endothelial cells and inhibits angiogenesis

Blood ◽  
2010 ◽  
Vol 116 (16) ◽  
pp. 3099-3107 ◽  
Author(s):  
Masashi Narazaki ◽  
Marta Segarra ◽  
Xu Hou ◽  
Toshio Tanaka ◽  
Xuri Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Receptor Internalization ◽  
Cell Surface Receptor ◽  
Ligand Interaction ◽  
Surface Receptors ◽  
Neuropilin 1 ◽  
And Function

Abstract Ligand interaction with cognate cell-surface receptor often promotes receptor internalization, protecting cells from prolonged or excessive signaling from extracellular ligands. Compounds that induce internalization of surface receptors prevent ligand binding to cognate cell-surface receptors serving as inhibitors. Here, we show that synthetic polyriboguanosine (poly G) and oligo-deoxyriboguanosine (oligo G) reduce endothelial levels of surface neuropilin-1 (NRP1), a receptor shared by semaphorin 3A and vascular endothelial growth factor (VEGF), which plays critical roles in angiogenesis. Oligo G also reduces levels of cell-surface scavenger receptor expressed by endothelial cells I (SREC-I), but not levels of NRP2, gp130, CD31, VEGFR-1, or VEGFR-2. Poly or oligo A, T, and C do not promote NRP1 or SREC-I internalization. We find that oligo G binds to NRP1 with high affinity (Kd:1.3 ± 0.16nM), bridges the extracellular domain of NRP1 to that of SREC-I, and induces coordinate internalization of NRP1 and SREC-I. In vitro, oligo G blocks the binding and function of VEGF165 in endothelial cells. In vivo, intravitreal administration of oligo G reduces choroidal neovascularization in mice. These results demonstrate that synthetic oligo G is an inhibitor of pathologic angiogenenesis that reduces cell-surface levels and function of NRP1 acting as an internalization inducer.

scholarly journals Targeting Integrins in Cancer Nanomedicine: Applications in Cancer Diagnosis and Therapy

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1783 ◽  
Author(s):  
Ping-Hsiu Wu ◽  
Abayomi Emmanuel Opadele ◽  
Yasuhito Onodera ◽  
Jin-Min Nam
Keyword(s):  
Cell Surface ◽  
Cancer Cells ◽  
Cancer Diagnostics ◽  
Migration And Invasion ◽  
Surface Receptors ◽  
Nanosized Materials ◽  
Tumor Microvasculature ◽  
Cancer Nanomedicine ◽  
New Treatment ◽  
And Function

Due to advancements in nanotechnology, the application of nanosized materials (nanomaterials) in cancer diagnostics and therapeutics has become a leading area in cancer research. The decoration of nanomaterial surfaces with biological ligands is a major strategy for directing the actions of nanomaterials specifically to cancer cells. These ligands can bind to specific receptors on the cell surface and enable nanomaterials to actively target cancer cells. Integrins are one of the cell surface receptors that regulate the communication between cells and their microenvironment. Several integrins are overexpressed in many types of cancer cells and the tumor microvasculature and function in the mediation of various cellular events. Therefore, the surface modification of nanomaterials with integrin-specific ligands not only increases their binding affinity to cancer cells but also enhances the cellular uptake of nanomaterials through the intracellular trafficking of integrins. Moreover, the integrin-specific ligands themselves interfere with cancer migration and invasion by interacting with integrins, and this finding provides a novel direction for new treatment approaches in cancer nanomedicine. This article reviews the integrin-specific ligands that have been used in cancer nanomedicine and provides an overview of the recent progress in cancer diagnostics and therapeutic strategies involving the use of integrin-targeted nanomaterials.

scholarly journals Early detachment of colon carcinoma cells during CD95(APO-1/Fas)-mediated apoptosis. I. De-adhesion from hyaluronate by shedding of CD44.

1996 ◽  
Vol 134 (4) ◽  
pp. 1089-1096 ◽  
Author(s):  
A R Günthert ◽  
J Sträter ◽  
U von Reyher ◽  
C Henne ◽  
S Joos ◽  
...  
Keyword(s):  
Cell Surface ◽  
Colon Carcinoma ◽  
Substantial Reduction ◽  
Carcinoma Cells ◽  
Surface Adhesion ◽  
Intact Cells ◽  
Surface Receptors ◽  
Colon Carcinoma Cells ◽  
Soluble Cd44

Ligation of CD95 (APO-1/Fas) cell surface receptors induces death in apoptosis-sensitive cells. Induction of apoptosis in adherent gamma interferon-stimulated HT-29 and COLO 205 colon carcinoma cells by cross-linking CD95 with anti-APO-1 monoclonal antibody resulted in detachment of the cells from hyaluronate starting about 1 h after antibody exposure. Loss of adhesion was paralleled by a substantial reduction of the multifunctional cell surface adhesion molecule CD44. As evidenced by cycloheximide treatment, this effect was not caused by impaired protein synthesis. Depletion of surface CD44 was also not due to membrane blebbing, since cytochalasin B failed to inhibit ascension from hyaluronate. Instead, ELISA and time kinetics showed increasing amounts of soluble CD44 in the supernatant of CD95-triggered cells. SDS-PAGE revealed that soluble CD44 had an apparent molecular mass of about 20 kD less than CD44 immunoprecipitated from intact cells. Thus, CD95-triggering induced shedding of CD44. Shedding is a novel mechanism operative in early steps of CD95-mediated apoptosis. Shedding surface molecules like CD44 might contribute to the active disintegration of dying epithelial cells in vivo.

scholarly journals Redirecting Retroviral Tropism by Insertion of Short, Nondisruptive Peptide Ligands into Envelope

2002 ◽  
Vol 76 (7) ◽  
pp. 3558-3563 ◽  
Author(s):  
Timothy J. Gollan ◽  
Michael R. Green
Keyword(s):  
Cell Surface ◽  
Leukemia Virus ◽  
Envelope Proteins ◽  
Peptide Ligands ◽  
Viral Envelope ◽  
Moloney Murine Leukemia Virus ◽  
Cell Surface Receptors ◽  
Wild Type ◽  
Surface Receptors

ABSTRACT A potentially powerful approach for in vivo gene delivery is to target retrovirus to specific cells through interactions between cell surface receptors and appropriately modified viral envelope proteins. Previously, relatively large (>100 residues) protein ligands to cell surface receptors have been inserted at or near the N terminus of retroviral envelope proteins. Although viral tropism could be altered, the chimeric envelope proteins lacked full activity, and coexpression of wild-type envelope was required for production of transducing virus. Here we analyze more than 40 derivatives of ecotropic Moloney murine leukemia virus (MLV) envelope, containing insertions of short RGD-containing peptides, which are ligands for integrin receptors. In many cases pseudotyped viruses containing only the chimeric envelope protein could transduce human cells. The precise location, size, and flanking sequences of the ligand affected transduction specificity and efficiency. We conclude that retroviral tropism can be rationally reengineered by insertion of short peptide ligands and without the need to coexpress wild-type envelope.

scholarly journals Sulfated polysaccharides identified as inducers of neuropilin-1 internalization and functional inhibition of VEGF165 and semaphorin3A

Blood ◽  
2008 ◽  
Vol 111 (8) ◽  
pp. 4126-4136 ◽  
Author(s):  
Masashi Narazaki ◽  
Marta Segarra ◽  
Giovanna Tosato
Keyword(s):  
Cell Surface ◽  
Dextran Sulfate ◽  
Receptor Internalization ◽  
Sulfated Polysaccharides ◽  
Cell Surface Receptors ◽  
Ligand Interaction ◽  
Surface Receptors ◽  
Neuropilin 1

Abstract Neuropilin-1 (NRP1) and NRP2 are cell surface receptors shared by class 3 semaphorins and vascular endothelial growth factor (VEGF). Ligand interaction with NRPs selects the specific signal transducer, plexins for semaphorins or VEGF receptors for VEGF, and promotes NRP internalization, which effectively shuts down receptor-mediated signaling by a second ligand. Here, we show that the sulfated polysaccharides dextran sulfate and fucoidan, but not others, reduce endothelial cell-surface levels of NRP1, NRP2, and to a lesser extent VEGFR-1 and VEGFR-2, and block the binding and in vitro function of semaphorin3A and VEGF165. Administration of fucoidan to mice reduces VEGF165-induced angiogenesis and tumor neovascularization in vivo. We find that dextran sulfate and fucoidan can bridge the extracellular domain of NRP1 to that of the scavenger receptor expressed by endothelial cells I (SREC-I), and induce NRP1 and SREC-I coordinate internalization and trafficking to the lysosomes. Overexpression of SREC-I in SREC-I–negative cells specifically reduces cell-surface levels of NRP1, indicating that SREC-I mediates NRP1 internalization. These results demonstrate that engineered receptor internalization is an effective strategy for reducing levels and function of cell-surface receptors, and identify certain sulfated polysaccharides as “internalization inducers.”

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