scholarly journals Intracellular Delivery of Active Proteins by Polyphosphazene Polymers

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 249
Author(s):  
Bareera Qamar ◽  
Melani Solomon ◽  
Alexander Marin ◽  
Thomas R. Fuerst ◽  
Alexander K. Andrianov ◽  
...  
Keyword(s):  
Intracellular Delivery ◽  
Protein Therapeutics ◽  
Cell Permeabilization ◽  
Protein Uptake ◽  
Cytosolic Delivery ◽  
Model Protein ◽  
A Cell ◽  
Internalization Rate ◽  
Great Relevance ◽  
Non Covalent Interactions

Achieving intracellular delivery of protein therapeutics within cells remains a significant challenge. Although custom formulations are available for some protein therapeutics, the development of non-toxic delivery systems that can incorporate a variety of active protein cargo and maintain their stability, is a topic of great relevance. This study utilized ionic polyphosphazenes (PZ) that can assemble into supramolecular complexes through non-covalent interactions with different types of protein cargo. We tested a PEGylated graft copolymer (PZ-PEG) and a pyrrolidone containing linear derivative (PZ-PYR) for their ability to intracellularly deliver FITC-avidin, a model protein. In endothelial cells, PZ-PYR/protein exhibited both faster internalization and higher uptake levels than PZ-PEG/protein, while in cancer cells both polymers achieved similar uptake levels over time, although the internalization rate was slower for PZ-PYR/protein. Uptake was mediated by endocytosis through multiple mechanisms, PZ-PEG/avidin colocalized more profusely with endo-lysosomes, and PZ-PYR/avidin achieved greater cytosolic delivery. Consequently, a PZ-PYR-delivered anti-F-actin antibody was able to bind to cytosolic actin filaments without needing cell permeabilization. Similarly, a cell-impermeable Bax-BH3 peptide known to induce apoptosis, decreased cell viability when complexed with PZ-PYR, demonstrating endo-lysosomal escape. These biodegradable PZs were non-toxic to cells and represent a promising platform for drug delivery of protein therapeutics.

Intracellular delivery of a native functional protein using cell-penetrating peptide functionalized cubic MSNs with ultra-large mesopores

2018 ◽  
Vol 6 (21) ◽  
pp. 3456-3465 ◽  
Author(s):  
Sang-Eun Bae ◽  
Soo Kyung Lyu ◽  
Ki-Jung Kim ◽  
Hee Joo Shin ◽  
Hyockman Kwon ◽  
...  
Keyword(s):  
Click Reaction ◽  
Intracellular Delivery ◽  
Cell Penetrating Peptide ◽  
Functional Protein ◽  
Native Form ◽  
Cytosolic Delivery ◽  
Cell Penetrating ◽  
A Cell ◽  
Large Mesopores

Pore-enlarged 3D cubic cMSNs were successfully prepared, and their surfaces were functionalized by a cell-penetrating R8-peptide through the click reaction for cytosolic delivery of a functional protein in its native form.

scholarly journals Cytosolic Delivery of Argininosuccinate Synthetase Using a Cell-Permeant Miniature Protein

2021 ◽  
Vol 7 (4) ◽  
pp. 641-649
Author(s):  
Susan L. Knox ◽  
Rebecca Wissner ◽  
Samantha Piszkiewicz ◽  
Alanna Schepartz
Keyword(s):  
Argininosuccinate Synthetase ◽  
Cytosolic Delivery ◽  
A Cell

Studies of the uptake of macromolecules by cells. I. Uptake of proteins by cells of the Ehrlich–Lettré ascites carcinoma

1968 ◽  
Vol 46 (12) ◽  
pp. 1443-1450 ◽  
Author(s):  
Y. C. Choi ◽  
E. R. M. Kay
Keyword(s):  
Nucleic Acid ◽  
Cell Membrane ◽  
Binding Sites ◽  
Specific Binding ◽  
Protein Uptake ◽  
Specific Binding Sites ◽  
Model Protein ◽  
Uptake Process ◽  
Kinetics Of ◽  
Protein Treatment

The uptake of protein by cells of the Ehrlich–Lettré ascites carcinoma was characterized kinetically by using hemoglobin as a model protein. An attempt was made to show that the process is not an artefact due to nonspecific adsorption of protein to the cell membrane. The kinetics of the uptake process suggested that an interaction exists between the exogenous protein and specific binding sites on the membrane. Acetylation of hemoglobin enhanced the rate of uptake of this protein. Treatment of cells with neuraminidase, phospholipase A, and Pronase resulted in an inhibition of protein uptake. The experimental evidence for the uptake of hemoglobin was supported by evidence that L-serine-U-14C-labelled hemoglobin is transported into the cytoplasm and utilized subsequently, resulting in labelling of the nucleic acid nucleotides.

scholarly journals A boronic acid–rich dendrimer with robust and unprecedented efficiency for cytosolic protein delivery and CRISPR-Cas9 gene editing

2019 ◽  
Vol 5 (6) ◽  
pp. eaaw8922 ◽  
Author(s):  
Chongyi Liu ◽  
Tao Wan ◽  
Hui Wang ◽  
Song Zhang ◽  
Yuan Ping ◽  
...  
Keyword(s):  
Boronic Acid ◽  
Protein Delivery ◽  
High Efficiency ◽  
Intracellular Delivery ◽  
Cytosolic Protein ◽  
Native Proteins ◽  
Cytosolic Delivery ◽  
Cas9 Protein ◽  
Cargo Proteins ◽  
Positively Charged

Cytosolic protein delivery is of central importance for the development of protein-based biotechnologies and therapeutics; however, efficient intracellular delivery of native proteins remains a challenge. Here, we reported a boronic acid–rich dendrimer with unprecedented efficiency for cytosolic delivery of native proteins. The dendrimer could bind with both negatively and positively charged proteins and efficiently delivered 13 cargo proteins into the cytosol of living cells. All the delivered proteins kept their bioactivities after cytosolic delivery. The dendrimer ensures efficient intracellular delivery of Cas9 protein into various cell lines and showed high efficiency in CRISPR-Cas9 genome editing. The rationally designed boronic acid–rich dendrimer permits the development of an efficient platform with high generality for the delivery of native proteins.

scholarly journals Codelivery of a cytotoxin and photosensitiser via a liposomal nanocarrier: a novel strategy for light-triggered cytosolic release

Nanoscale ◽  
2018 ◽  
Vol 10 (43) ◽  
pp. 20366-20376 ◽  
Author(s):  
Elnaz Yaghini ◽  
Ruggero Dondi ◽  
Karen J. Edler ◽  
Marilena Loizidou ◽  
Alexander J. MacRobert ◽  
...  
Keyword(s):  
Intracellular Delivery ◽  
Cell Penetrating Peptide ◽  
Protein Toxin ◽  
Cell Penetrating ◽  
A Cell ◽  
Novel Strategy

Light-triggered intracellular delivery of a protein toxin was achieved by codelivery via a liposomal nanocarrier, targeted with a cell-penetrating peptide (CPP)–photosensitiser conjugate.

scholarly journals Intracellular Delivery of a Cell-Penetrating SOCS1 that Targets IFN-  Signaling

2009 ◽  
Vol 2 (80) ◽  
pp. ra37-ra37 ◽  
Author(s):  
A. DiGiandomenico ◽  
L. S. Wylezinski ◽  
J. Hawiger
Keyword(s):  
Intracellular Delivery ◽  
Cell Penetrating ◽  
A Cell

Supramolecular intracellular delivery of an anionic porphyrin by octaarginine-conjugated per-O-methyl-β-cyclodextrin

2015 ◽  
Vol 51 (12) ◽  
pp. 2421-2424 ◽  
Author(s):  
Hiroaki Kitagishi ◽  
Fumihiko Chai ◽  
Shigeru Negi ◽  
Yukio Sugiura ◽  
Koji Kano
Keyword(s):  
Efficient Method ◽  
Intracellular Delivery ◽  
Water Soluble ◽  
Cell Penetrating Peptide ◽  
Supramolecular Interaction ◽  
Cell Penetrating ◽  
A Cell

A convenient and efficient method for intracellular delivery of a water-soluble anionic porphyrin has been developed by utilizing its supramolecular interaction with per-O-methyl-β-cyclodextrin bearing an octaarginine chain as a cell-penetrating peptide.

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