scholarly journals Cellular Uptake and Cytosolic Delivery of a Cyclic Cystine Knot Scaffold

2020 ◽  
Vol 15 (6) ◽  
pp. 1650-1661 ◽  
Author(s):  
Huawu Yin ◽  
Yen-Hua Huang ◽  
Kirsten Deprey ◽  
Nicholas D. Condon ◽  
Joshua A. Kritzer ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Cystine Knot ◽  
Cytosolic Delivery

scholarly journals Diselenolane‐Mediated Cellular Uptake: Efficient Cytosolic Delivery of Probes, Peptides, Proteins, Artificial Metalloenzymes and Protein‐Coated Quantum Dots

2019 ◽  
Vol 25 (16) ◽  
pp. 4047-4051 ◽  
Author(s):  
Eline Bartolami ◽  
Dimitris Basagiannis ◽  
Lili Zong ◽  
Rémi Martinent ◽  
Yasunori Okamoto ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Cellular Uptake ◽  
Cytosolic Delivery ◽  
Artificial Metalloenzymes

scholarly journals Cationic poly(amidoamine) promotes cytosolic delivery of bovine RNase A in melanoma cells, while maintaining its cellular toxicity

2015 ◽  
Vol 3 (31) ◽  
pp. 6501-6508 ◽  
Author(s):  
Julie L. N. Dubois ◽  
Nathalie Lavignac
Keyword(s):  
Cell Death ◽  
Cellular Uptake ◽  
Melanoma Cells ◽  
Rnase A ◽  
Wild Type ◽  
Cellular Toxicity ◽  
Cytosolic Delivery

Poly(amidoamine)s enhance cellular uptake of wild-type RNase A in B16F1 melanoma cells and help its cytosolic delivery, inducing increased cell death.

scholarly journals Cellular Uptake and Cytosolic Delivery of a Cyclic Cystine Knot Scaffold

2020 ◽  
Author(s):  
Huawu Yin ◽  
Yen-Hua Huang ◽  
Kirsten Deprey ◽  
Nicholas Condon ◽  
Joshua Kritzer ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Therapeutic Potential ◽  
Hydrophobic Amino Acid ◽  
Kalata B1 ◽  
Cytosolic Delivery ◽  
Intracellular Proteins ◽  
Macrocyclic Peptides ◽  
Low Efficiency ◽  
Further Development ◽  
Stable Structures

Cyclotides are macrocyclic peptides that have exceptionally stable structures and been reported to penetrate cells, making them promising scaffolds for the delivery of peptide inhibitory sequences to target intracellular proteins. However, their cellular uptake and cytosolic localization have been poorly understood until now, which has limited their therapeutic potential. In this study, the recently developed chloroalkane penetration assay was combined with established assays to characterize the cellular uptake and cytosolic delivery of the prototypic cyclotide, kalata B1. We show that kalata B1 enters the cytosol at low efficiency, but introducing various epitopes, including a single hydrophobic amino acid, into its loop 6 significantly improved its cytosolic delivery. Our results provide a foundation for the further development of a structurally unique class of scaffolds for the delivery of therapeutic cargoes into cells.<br>

scholarly journals Cellular uptake of a cystine-knot peptide and modulation of its intracellular trafficking

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Xinxin Gao ◽  
Karen Stanger ◽  
Harini Kaluarachchi ◽  
Till Maurer ◽  
Paulina Ciepla ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Intracellular Trafficking ◽  
Cystine Knot

scholarly journals Diselenolane-mediated cellular uptake

2018 ◽  
Vol 9 (7) ◽  
pp. 1860-1866 ◽  
Author(s):  
Nicolas Chuard ◽  
Amalia I. Poblador-Bahamonde ◽  
Lili Zong ◽  
Eline Bartolami ◽  
Jana Hildebrandt ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Dihedral Angles ◽  
Cytosolic Delivery

Selenophilicity, minimized dihedral angles, acidic selenols, multitarget hopping: cytosolic delivery with 1,2-diselenolanes outperforms 1,2-dithiolanes, by far.

Cellular Uptake and Cytosolic Delivery of a Cyclic Cystine Knot Scaffold

2020 ◽  
Author(s):  
Huawu Yin ◽  
Yen-Hua Huang ◽  
Kirsten Deprey ◽  
Nicholas Condon ◽  
Joshua Kritzer ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Therapeutic Potential ◽  
Hydrophobic Amino Acid ◽  
Kalata B1 ◽  
Cytosolic Delivery ◽  
Intracellular Proteins ◽  
Macrocyclic Peptides ◽  
Low Efficiency ◽  
Further Development ◽  
Stable Structures

Cyclotides are macrocyclic peptides that have exceptionally stable structures and been reported to penetrate cells, making them promising scaffolds for the delivery of peptide inhibitory sequences to target intracellular proteins. However, their cellular uptake and cytosolic localization have been poorly understood until now, which has limited their therapeutic potential. In this study, the recently developed chloroalkane penetration assay was combined with established assays to characterize the cellular uptake and cytosolic delivery of the prototypic cyclotide, kalata B1. We show that kalata B1 enters the cytosol at low efficiency, but introducing various epitopes, including a single hydrophobic amino acid, into its loop 6 significantly improved its cytosolic delivery. Our results provide a foundation for the further development of a structurally unique class of scaffolds for the delivery of therapeutic cargoes into cells.<br>

scholarly journals Pharmacological Activation of cGAS for Cancer Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Kyle M. Garland ◽  
Jonah C. Rosch ◽  
Carcia S. Carson ◽  
Lihong Wang-Bishop ◽  
Ann Hanna ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Antitumor Immunity ◽  
Immune Checkpoint Blockade ◽  
Endosomal Escape ◽  
Double Stranded Dna ◽  
Cytosolic Delivery ◽  
Immune Mediated ◽  
Immunotherapeutic Strategy ◽  
Cellular Signaling Pathway ◽  
Sting Pathway

When compartmentally mislocalized within cells, nucleic acids can be exceptionally immunostimulatory and can even trigger the immune-mediated elimination of cancer. Specifically, the accumulation of double-stranded DNA in the cytosol can efficiently promote antitumor immunity by activating the cGAMP synthase (cGAS) / stimulator of interferon genes (STING) cellular signaling pathway. Targeting this cytosolic DNA sensing pathway with interferon stimulatory DNA (ISD) is therefore an attractive immunotherapeutic strategy for the treatment of cancer. However, the therapeutic activity of ISD is limited by several drug delivery barriers, including susceptibility to deoxyribonuclease degradation, poor cellular uptake, and inefficient cytosolic delivery. Here, we describe the development of a nucleic acid immunotherapeutic, NanoISD, which overcomes critical delivery barriers that limit the activity of ISD and thereby promotes antitumor immunity through the pharmacological activation of cGAS at the forefront of the STING pathway. NanoISD is a nanoparticle formulation that has been engineered to confer deoxyribonuclease resistance, enhance cellular uptake, and promote endosomal escape of ISD into the cytosol, resulting in potent activation of the STING pathway via cGAS. NanoISD mediates the local production of proinflammatory cytokines via STING signaling. Accordingly, the intratumoral administration of NanoISD induces the infiltration of natural killer cells and T lymphocytes into murine tumors. The therapeutic efficacy of NanoISD is demonstrated in preclinical tumor models by attenuated tumor growth, prolonged survival, and an improved response to immune checkpoint blockade therapy.

Water-soluble amphiphilic ruthenium(ii) polypyridyl complexes as potential light-activated therapeutic agents

2020 ◽  
Vol 56 (65) ◽  
pp. 9332-9335
Author(s):  
Sandra Estalayo-Adrián ◽  
Salvador Blasco ◽  
Sandra A. Bright ◽  
Gavin J. McManus ◽  
Guillermo Orellana ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Therapeutic Agents ◽  
Water Soluble ◽  
Polypyridyl Complexes ◽  
Cervical Cancer Cells

Two new water-soluble amphiphilic Ru(ii) polypyridyl complexes were synthesised and their photophysical and photobiological properties evaluated; both complexes showed a rapid cellular uptake and phototoxicity against HeLa cervical cancer cells.

New cystine knot peptides from a marine sponge Asteropus sp.

Planta Medica ◽  
2010 ◽  
Vol 76 (12) ◽  
Author(s):  
J Jung ◽  
H Li ◽  
J Li ◽  
C Lee ◽  
W Lee ◽  
...  
Keyword(s):  
Marine Sponge ◽  
Cystine Knot
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