High-Loading Self-Assembling Peptide Nanoparticles as a Lipid-Free Carrier for Hydrophobic General Anesthetics

Peptide nanotechnology has experienced a long and enduring development since its inception. Many different applications have been conceptualized, which depends on the functional groups present on the peptide and the physical shape/size of the peptide nanostructures. One of the most prominent nanostructures formed by peptides are nanoparticles. Until recently, however, it has been challenging to engineer peptide nanoparticles with low dispersity. An emerging and promising technique involves the utility of microfluidics to produce a solution of peptide nanoparticles with narrow dispersity. In this process, two or more streams of liquid are focused together to create conditions that are conducive towards the formation of narrowly dispersed samples of peptide nanoparticles. This makes it possible to harness peptide nanoparticles for the myriad of applications that are dependent on nanoparticle size and uniformity. In this focus review, we aim to show how microfluidics may be utilized to (1) study peptide self-assembly, which is critical to controlling nanostructure shape and size, and peptide-interface interactions, and (2) generate self-assembling peptide-based microgels for miniaturized cell cultures. These examples will illustrate how the emerging microfluidic approach promises to revolutionize the production and application of peptide nanoparticles in ever more diverse fields than before.

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High-loading Gα13-binding EXE peptide nanoparticles prevent thrombosis and protect mice from cardiac ischemia/reperfusion injury

Science Translational Medicine ◽

10.1126/scitranslmed.aaz7287 ◽

2020 ◽

Vol 12 (552) ◽

pp. eaaz7287

Author(s):

Aiming Pang ◽

Ni Cheng ◽

Yujie Cui ◽

Yanyan Bai ◽

Zhigang Hong ◽

...

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Bleeding Risk ◽

High Loading ◽

Myocardial Ischemia Reperfusion Injury ◽

Peptide Nanoparticles ◽

Myocardial Ischemia Reperfusion

Inefficient delivery is a major obstacle to the development of peptide-based drugs targeting the intracellular compartment. We recently showed that selectively inhibiting integrin outside-in signaling using a peptide (mP6) derived from the Gα13-binding ExE motif within the integrin β3 cytoplasmic domain had antithrombotic effects. Here, we engineered lipid-stabilized, high-loading peptide nanoparticles (HLPN), in which a redesigned ExE peptide (M3mP6) constituted up to 70% of the total nanoparticle molarity, allowing efficient in vivo delivery. We observed that M3mP6 HLPN inhibited occlusive thrombosis more potently than a clopidogrel/aspirin combination without adverse effects on hemostasis in rodents. Furthermore, M3mP6 HLPN synergized with P2Y12 receptor inhibitors or the clopidogrel/aspirin combination in preventing thrombosis, without exacerbating hemorrhage. M3mP6 HLPN also inhibited intravascular coagulation more potently than the P2Y12 inhibitor cangrelor. Postischemia injection of M3mP6 HLPN protected the heart from myocardial ischemia–reperfusion injury in a mouse model. This study demonstrates an efficient in vivo peptide delivery strategy for a therapeutic that not only efficaciously prevented thrombosis with minimal bleeding risk but also protected from myocardial ischemia–reperfusion injury in mice.

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Preparation and printability of ultrashort self-assembling peptide nanoparticles

International Journal of Bioprinting ◽

10.18063/ijb.v5i2.239 ◽

2019 ◽

Vol 5 (2) ◽

Cited By ~ 1

Author(s):

Sarah Ghalayini ◽

Hepi Hari Susapto ◽

Sophie Hall ◽

Kowther Kahin ◽

Charlotte Hauser

Keyword(s):

Three Dimensional ◽

The Body ◽

Cell Labeling ◽

Self Assembling ◽

3D Printed ◽

Peptide Nanoparticles ◽

Materials Used ◽

Long Term Studies

Nanoparticles (NPs) have left their mark on the field of bioengineering. Fabricated from metallic, magnetic, and metal oxide materials, their applications include drug delivery, bioimaging, and cell labeling. However, as they enter the body, the question remains – where do they go after fulfilling their designated function? As most materials used to produce NPs are not naturally found in the body, they are not biodegradable and may accumulate overtime. There is a lack of comprehensive, long-term studies assessing the biodistribution of non-biodegradable NPs for even the most widely studied NPs. There is a clear need for NPs produced from natural materials capable of degradation in vivo. As peptides exist naturally within the human body, their non-toxic and biocompatible nature comes as no surprise. Ultrashort peptides are aliphatic peptides designed with three to seven amino acids capable of self-assembling into helical fibers within macromolecular structures. Using a microfluidics flow-focusing approach, we produced different peptide-based NPs that were then three-dimensional (3D) printed with our novel printer setup. Herein, we describe the preparation method of NPs from ultrashort self-assembling peptides and their morphology in both manual and 3D-printed hydrogels, thus suggesting that peptide NPs are capable of withstanding the stresses involved in the printing process

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Torus Circumference and Thickness Parameters From a Linear DNA Size Series Suggest How Toruses Self-Assemble

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100119430 ◽

1985 ◽

Vol 43 ◽

pp. 522-523

Author(s):

George C. Ruben ◽

Kenneth A. Marx

Keyword(s):

Tertiary Structure ◽

Dna Complexes ◽

Tertiary Structures ◽

Self Assembling ◽

Double Stranded Dna ◽

Calf Thymus ◽

Dna Organization ◽

Condensed Dna ◽

Dna Size

Certain double stranded DNA bacteriophage and viruses are thought to have their DNA organized into large torus shaped structures. Morphologically, these poorly understood biological DNA tertiary structures resemble spermidine-condensed DNA complexes formed in vitro in the total absence of other macromolecules normally synthesized by the pathogens for the purpose of their own DNA packaging. Therefore, we have studied the tertiary structure of these self-assembling torus shaped spermidine- DNA complexes in a series of reports. Using freeze-etch, low Pt-C metal (10-15Å) replicas, we have visualized the microscopic DNA organization of both calf Thymus( CT) and linear 0X-174 RFII DNA toruses. In these structures DNA is circumferentially wound, continuously, around the torus into a semi-crystalline, hexagonal packed array of parallel DNA helix sections.

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Effects of dopant concentration on the microstructure of tin- doped indium oxide thin films

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010017671x ◽

1990 ◽

Vol 48 (4) ◽

pp. 716-717

Author(s):

I. A. Rauf

Keyword(s):

Thin Films ◽

Indium Oxide ◽

Ionic Radius ◽

Free Carrier ◽

Electron Gun ◽

Periodic Lattice ◽

Oxide Thin Films ◽

Transmission Electron ◽

The Difference ◽

Dopant Atoms

To understand the electronic conduction mechanism in Sn-doped indium oxide thin films, it is important to study the effect of dopant atoms on the neighbouring indium oxide lattice. Ideally Sn is a substitutional dopant at random indium sites. The difference in valence (Sn4+ replaces In3+) requires that an extra electron is donated to the lattice and thus contributes to the free carrier density. But since Sn is an adjacent member of the same row in the periodic table, the difference in the ionic radius (In3+: 0.218 nm; Sn4+: 0.205 nm) will introduce a strain in the indium oxide lattice. Free carrier electron waves will no longer see a perfect periodic lattice and will be scattered, resulting in the reduction of free carrier mobility, which will lower the electrical conductivity (an undesirable effect in most applications).One of the main objectives of the present investigation is to understand the effects of the strain (produced by difference in the ionic radius) on the microstructure of the indium oxide lattice when the doping level is increased to give high carrier densities. Sn-doped indium oxide thin films were prepared with four different concentrations: 9, 10, 11 and 12 mol. % of SnO2 in the starting material. All the samples were prepared at an oxygen partial pressure of 0.067 Pa and a substrate temperature of 250°C using an Edwards 306 coating unit with an electron gun attachment for heating the crucible. These deposition conditions have been found to give optimum electrical properties in Sn-doped indium oxide films. A JEOL 2000EX transmission electron microscope was used to investigate the specimen microstructure.

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