Modifying Cell Membranes with Anionic Polymer Amphiphiles Potentiates Intracellular Delivery of Cationic Peptides

2020 ◽  
Vol 12 (45) ◽  
pp. 50222-50235
Author(s):  
Eric A. Dailing ◽  
Kameron V. Kilchrist ◽  
J. William Tierney ◽  
R. Brock Fletcher ◽  
Brian C. Evans ◽  
...  
1999 ◽  
Vol 5 (S2) ◽  
pp. 392-393
Author(s):  
Joan F. Karr ◽  
Robert P. Apkarian ◽  
John A. Petros

Transfection of mammalian cells can be enhanced by forming complexes between exogenous DNA and cationic peptides which facilitate DNA transport through cell membranes. Although complexes of plasmid DNA and cationic peptides have been characterized by microscopy, little is known about the complexes formed between oligonucleotides (ODN) and cationic peptides or how the ultrastructure of these complexes affects the intracellular delivery via the cell membrane. Because ODN have potential as therapeutic reagents in the treatment of many diseases, there is a need to develop improved methods for effective delivery of these molecules. By analyzing molecular interactions between cationic peptides and ODN and their effects on cell membranes, cell viability, and DNA delivery, improved delivery compounds can be designed. In this paper, we compare the interactions of a 28 base ODN with three cationic peptides: a novel compound, MNLEK (H-Met-(Nle-Lys4)7-Nle-NH2), an established transfection reagent, poly(L-lysine) (∼ 54 kDa), and a recently described cationic peptide which delivers both plasmid DNA and antisense ODN to cells, KALA (WEAKLAKALAKALAKHLAKALAKALKACEA).For high resolution scanning electron microscopy (HRSEM), DU145 human prostate cancer cells were grown overnight on poly-(D-lysine) coated, UV irradiated silicon chips.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Brian C. Evans ◽  
R. Brock Fletcher ◽  
Kameron V. Kilchrist ◽  
Eric A. Dailing ◽  
Alvin J. Mukalel ◽  
...  

Abstract Peptides and biologics provide unique opportunities to modulate intracellular targets not druggable by conventional small molecules. Most peptides and biologics are fused with cationic uptake moieties or formulated into nanoparticles to facilitate delivery, but these systems typically lack potency due to low uptake and/or entrapment and degradation in endolysosomal compartments. Because most delivery reagents comprise cationic lipids or polymers, there is a lack of reagents specifically optimized to deliver cationic cargo. Herein, we demonstrate the utility of the cytocompatible polymer poly(propylacrylic acid) (PPAA) to potentiate intracellular delivery of cationic biomacromolecules and nano-formulations. This approach demonstrates superior efficacy over all marketed peptide delivery reagents and enhances delivery of nucleic acids and gene editing ribonucleoproteins (RNPs) formulated with both commercially-available and our own custom-synthesized cationic polymer delivery reagents. These results demonstrate the broad potential of PPAA to serve as a platform reagent for the intracellular delivery of cationic cargo.


Author(s):  
A. Tonosaki ◽  
M. Yamasaki ◽  
H. Washioka ◽  
J. Mizoguchi

A vertebrate disk membrane is composed of 40 % lipids and 60 % proteins. Its fracture faces have been classed into the plasmic (PF) and exoplasmic faces (EF), complementary with each other, like those of most other types of cell membranes. The hypothesis assuming the PF particles as representing membrane-associated proteins has been challenged by serious questions if they in fact emerge from the crystalline formation or decoration effects during freezing and shadowing processes. This problem seems to be yet unanswered, despite the remarkable case of the purple membrane of Halobacterium, partly because most observations have been made on the replicas from a single face of specimen, and partly because, in the case of photoreceptor membranes, the conformation of a rhodopsin and its relatives remains yet uncertain. The former defect seems to be partially fulfilled with complementary replica methods.


Author(s):  
R.J. Barrnett

This subject, is like observing the panorama of a mountain range, magnificent towering peaks, but it doesn't take much duration of observation to recognize that they are still in the process of formation. The mountains consist of approaches, materials and methods and the rocky substance of information has accumulated to such a degree that I find myself concentrating on the foothills in the foreground in order to keep up with the advance; the edifices behind form a wonderous, substantive background. It's a short history for such an accumulation and much of it has been moved by the members of the societies that make up this International Federation. My panel of speakers are here to provide what we hope is an interesting scientific fare, based on the fact that there is a continuum of biological organization from biochemical molecules through macromolecular assemblies and cellular membranes to the cell itself. Indeed, this fact explains the whole range of towering peaks that have emerged progressively during the past 25 years.


2007 ◽  
Vol 177 (4S) ◽  
pp. 223-223
Author(s):  
Sreenivasa R. Chinni ◽  
Hamilto Yamamoto ◽  
Zhong Dong ◽  
Aaron Sabbota ◽  
Sanaa Nabha ◽  
...  

2018 ◽  
Vol 1 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Darío Acuña-Castroviejo ◽  
Maria T Noguiera-Navarro ◽  
Russel J Reiter ◽  
Germaine Escames

Due to the broad distribution of extrapineal melatonin in multiple organs and tissues, we analyzed the presence and subcellular distribution of the indoleamine in the heart of rats. Groups of sham-operated and pinealectomized rats were sacrificed at different times along the day, and the melatonin content in myocardial cell membranes, cytosol, nuclei and mitochondria, were measured. Other groups of control animals were treated with different doses of melatonin to monitor its intracellular distribution. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondria vary along the day, without showing a circadian rhythm. Pinealectomized animals trend to show higher values than sham-operated rats. Exogenous administration of melatonin yields its accumulation in a dose-dependent manner in all subcellular compartments analyzed, with maximal concentrations found in cell membranes at doses of 200 mg/kg bw melatonin. Interestingly, at dose of 40 mg/kg b.w, maximal concentration of melatonin was reached in the nucleus and mitochondrion. The results confirm previous data in other rat tissues including liver and brain, and support that melatonin is not uniformly distributed in the cell, whereas high doses of melatonin may be required for therapeutic purposes.


TAPPI Journal ◽  
2009 ◽  
Vol 8 (6) ◽  
pp. 29-35 ◽  
Author(s):  
PEDRAM FATEHI ◽  
LIYING QIAN ◽  
RATTANA KITITERAKUN ◽  
THIRASAK RIRKSOMBOON ◽  
HUINING XIAO

The application of an oppositely charged dual polymer system is a promising approach to enhance paper strength. In this work, modified chitosan (MCN), a cationic polymer, and carboxymethyl cellulose (CMC), an anionic polymer, were used sequentially to improve paper strength. The adsorption of MCN on cellulose fibers was analyzed via polyelectrolyte titration. The formation of MCN/CMC complex in water and the deposition of this complex on silicon wafers were investigated by means of atomic force microscope and quasi-elastic light scattering techniques. The results showed that paper strength was enhanced slightly with a layer-by-layer assembly of the polymers. However, if the washing stage, which was required for layer-by-layer assembly, was eliminated, the MCN/CMC complex was deposited on fibers more efficiently, and the paper strength was improved more significantly. The significant improvement was attributed to the extra development of fiber bonding, confirmed further by scanning electron microscope observation of the bonding area of fibers treated with or without washing. However, the brightness of papers was somewhat decreased by the deposition of the complex on fibers. Higher paper strength also was achieved using rapid drying rather than air drying.


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