scholarly journals Towards Developing Bioresponsive, Self-Assembled Peptide Materials: Dynamic Morphology and Fractal Nature of Nanostructured Matrices

Materials ◽  
2018 ◽  
Vol 11 (9) ◽  
pp. 1539 ◽  
Author(s):  
Kyle Koss ◽  
Larry Unsworth
Keyword(s):  
Fine Structure ◽  
Focal Point ◽  
Peptide Delivery ◽  
Bioactive Molecules ◽  
Matrix Metalloproteinase 2 ◽  
Fractal Nature ◽  
Self Assembling ◽  
Delivery Platform ◽  
Peptide Materials ◽  
Novel Strategy

(Arginine-alanine-aspartic acid-alanine)4 ((RADA)4) nanoscaffolds are excellent candidates for use as peptide delivery vehicles: they are relatively easy to synthesize with custom bio-functionality, and assemble in situ to allow a focal point of release. This enables (RADA)4 to be utilized in multiple release strategies by embedding a variety of bioactive molecules in an all-in-one “construct”. One novel strategy focuses on the local, on-demand release of peptides triggered via proteolysis of tethered peptide sequences. However, the spatial-temporal morphology of self-assembling nanoscaffolds may greatly influence the ability of enzymes to both diffuse into as well as actively cleave substrates. Fine structure and its impact on the overall effect on peptide release is poorly understood. In addition, fractal networks observed in nanoscaffolds are linked to the fractal nature of diffusion in these systems. Therefore, matrix morphology and fractal dimension of virgin (RADA)4 and mixtures of (RADA)4 and matrix metalloproteinase 2 (MMP-2) cleavable substrate modified (RADA)4 were characterized over time. Sites of high (glycine-proline-glutamine-glycine+isoleucine-alanine-serine-glutamine (GPQG+IASQ), CP1) and low (glycine-proline-glutamine-glycine+proline-alanine-glycine-glutamine (GPQG+PAGQ), CP2) cleavage activity were chosen. Fine structure was visualized using transmission electron microscopy. After 2 h of incubation, nanofiber networks showed an established fractal nature; however, nanofibers continued to bundle in all cases as incubation times increased. It was observed that despite extensive nanofiber bundling after 24 h of incubation time, the CP1 and CP2 nanoscaffolds were susceptible to MMP-2 cleavage. The properties of these engineered nanoscaffolds characterized herein illustrate that they are an excellent candidate as an enzymatically initiated peptide delivery platform.

scholarly journals Towards Developing Bioresponsive, Self-Assembled Peptide Materials: Dynamic Morphology and Fractal Nature of Nanostructured Matrices

2018 ◽  
Author(s):  
Kyle Koss ◽  
Larry Unsworth
Keyword(s):  
Fine Structure ◽  
Focal Point ◽  
Peptide Delivery ◽  
Bioactive Molecules ◽  
Matrix Metalloproteinase 2 ◽  
Fractal Nature ◽  
Self Assembling ◽  
Delivery Platform ◽  
Peptide Materials ◽  
Novel Strategy

(RADA)4 nanoscaffolds are excellent candidates for use as peptide delivery vehicles: they are relatively easy to synthesize with custom bio-functionality, and assemble in situ to allow a focal point of release. This enables (RADA)4 to be utilized in multiple release strategies by embedding a variety of bioactive molecules in an all-in-one ‘construct’. One novel strategy focuses on the local, on-demand release of peptides triggered via proteolysis of tethered peptide sequences. However, the spatial-temporal morphology of self-assembling nanoscaffolds may greatly influence the ability for enzymes to both diffuse into as well as actively cleave substrates. Fine structure and its impact on overall affect on peptide release is poorly understood. In addition, fractal networks observed in nanoscaffolds are linked to the fractal nature of diffusion in these systems. Therefore, matrix morphology and fractal dimension of virgin (RADA)4 and mixtures of (RADA)4 and matrix metalloproteinase 2 (MMP-2) cleavable substrate modified (RADA)4 were characterized over time. Sites of high (GPQG+IASQ, CP1) and low (GPQG+PAGQ, CP2) cleavage activity were chosen. Fine structure was visualized using established according to established methods. After 2 hrs of incubation, nanofiber networks showed an established fractal nature, however nanofibers continued to bundle in all cases as incubation times increased. It was observed that despite extensive nanofiber bundling after 24 hrs of incubation time, the CP1 and CP2 nanoscaffolds were susceptible to MMP-2 cleavage. The properties of these engineered nanoscaffolds characterized herein illustrate that they are an excellent candidate as an enzymatically initiated peptide delivery platform.

L cell stimulation: a novel strategy for oral peptide delivery in incretin-based diabetes treatment

2020 ◽  
Author(s):  
Ana Beloqui ◽  
Francesco Suriano ◽  
Matthias Hul ◽  
Yining Xu ◽  
Véronique Préat ◽  
...  
Keyword(s):  
Peptide Delivery ◽  
Diabetes Treatment ◽  
Cell Stimulation ◽  
Oral Peptide Delivery ◽  
L Cell ◽  
Novel Strategy

scholarly journals Self-assembling Peptide Discovery: Overcoming Human Bias With Machine Learning

2021 ◽  
Author(s):  
Rohit Batra ◽  
Troy Loeffler ◽  
Henry Chan ◽  
Srilok Sriniva ◽  
Honggang Cui ◽  
...  
Keyword(s):  
Machine Learning ◽  
Self Assembly ◽  
Search Space ◽  
Sequence Length ◽  
Monte Carlo Tree Search ◽  
Self Assembling ◽  
Naturally Occurring ◽  
Peptide Materials ◽  
Dynamics Simulations ◽  
Better Than

Abstract Peptide materials have a wide array of functions from tissue engineering, surface coatings to catalysis and sensing. This class of biopolymer is composed of a sequence, comprised of 20 naturally occurring amino acids whose arrangement dictate the peptide functionality. While it is highly desirable to tailor the amino acid sequence, a small increase in their sequence length leads to dramatic increase in the possible candidates (e.g., from tripeptide = 20^3 or 8,000 peptides to a pentapeptide = 20^5 or 3.2 M). Traditionally, peptide design is guided by the use of structural propensity tables, hydrophobicity scales, or other desired properties and typically yields <10 peptides per study, barely scraping the surface of the search space. These approaches, driven by human expertise and intuition, are not easily scalable and are riddled with human bias. Here, we introduce a machine learning workflow that combines Monte Carlo tree search and random forest, with molecular dynamics simulations to develop a fully autonomous computational search engine (named, AI-expert) to discover peptide sequences with high potential for self-assembly (as a representative target functionality). We demonstrate the efficacy of the AI-expert to efficiently search large spaces of tripeptides and pentapeptides. Subsequent experiments on the proposed peptide sequences are performed to compare the predictability of the AI-expert with those of human experts. The AI performs on-par or better than human experts and suggests several non-intuitive sequences with high self-assembly propensity, outlining its potential to overcome human bias and accelerate peptide discovery.

scholarly journals Gelation properties of self-assembling N-acyl modified cytidine derivatives

2014 ◽  
Vol 2 (47) ◽  
pp. 8412-8417 ◽  
Author(s):  
K. J. Skilling ◽  
A. Ndungu ◽  
B. Kellam ◽  
M. Ashford ◽  
T. D. Bradshaw ◽  
...  
Keyword(s):  
Binary Mixture ◽  
Organic Solvent ◽  
Self Assembling ◽  
Delivery Platform

A new design for a self-assembling gelator of cytidine containing a binary mixture of organic solvent and water, shown to provide a suitable delivery platform for high and low Mw molecules.

Systemic hypoxia potentiates anti-tumor effects of metformin in hepatocellular carcinoma in mice

2020 ◽  
Vol 52 (4) ◽  
pp. 421-429
Author(s):  
Hui Lin ◽  
Wenfang Zhou ◽  
Yonghong Huang ◽  
Min Ren ◽  
Fangyun Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Progression ◽  
Tumor Volume ◽  
Combined Treatment ◽  
Hypoxia Inducible Factor ◽  
Inhibitory Effect ◽  
Whole Body ◽  
Matrix Metalloproteinase 2 ◽  
Systemic Hypoxia ◽  
Novel Strategy

Abstract Local hypoxia is a universal phenomenon in most solid tumors. The role of local hypoxia in the tumor microenvironment and cancer growth and metastasis has been well established. However, the effect of acute systemic hypoxia (exposing the whole body to 10% O2 environment) on cancer has not yet been investigated. In this study, we investigated the potential effects of acute systemic hypoxia itself and in combination with metformin on hepatocellular carcinoma (HCC) growth and metastasis in a mouse model of HCC. Acute systemic hypoxia significantly decreased tumor volume and weight in H22 tumor-bearing mice. Interestingly, the combined treatment of acute systemic hypoxia and metformin showed a more pronounced effect in reducing tumor volume and weight. Moreover, acute systemic hypoxia and metformin in combination had a potent inhibitory effect on tumor progression. More importantly, the expressions of hypoxia response genes including hypoxia-inducible factor-1 α, vascular endothelial growth factor, and matrix metalloproteinase 2 were significantly decreased in the tumor tissues with combination treatment. Our study demonstrated that acute systemic hypoxia repressed tumor progression of the HCC and potentiated the anti-tumor activities of metformin. This study supports that combination of systemic hypoxia and metformin treatment may represent a novel strategy for HCC.

Self-assembling Peptides in Current Nanomedicine: Versatile Nanomaterials for Drug Delivery

2020 ◽  
Vol 27 (29) ◽  
pp. 4855-4881 ◽  
Author(s):  
Fei Peng ◽  
Wensheng Zhang ◽  
Feng Qiu
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Slow Release ◽  
Therapeutic Effects ◽  
Peptide Amphiphile ◽  
Self Assembling ◽  
Synthetic Materials ◽  
Peptide Materials ◽  
Structural Compatibility ◽  
Drug Complex

Background: The development of modern nanomedicine greatly depends on the involvement of novel materials as drug delivery system. In order to maximize the therapeutic effects of drugs and minimize their side effects, a number of natural or synthetic materials have been widely investigated for drug delivery. Among these materials, biomimetic self-assembling peptides (SAPs) have received more attention in recent years. Considering the rapidly growing number of SAPs designed for drug delivery, a summary of how SAPs-based drug delivery systems were designed, would be beneficial. Method: We outlined research works on different SAPs that have been investigated as carriers for different drugs, focusing on the design of SAPs nanomaterials and how they were used for drug delivery in different strategies. Results: Based on the principle rules of chemical complementarity and structural compatibility, SAPs such as ionic self-complementary peptide, peptide amphiphile and surfactant-like peptide could be designed. Determined by the features of peptide materials and the drugs to be delivered, different strategies such as hydrogel embedding, hydrophobic interaction, electrostatic interaction, covalent conjugation or the combination of them could be employed to fabricate SAPs-drug complex, which could achieve slow release, targeted or environment-responsive delivery of drugs. Furthermore, some SAPs could also be combined with other types of materials for drug delivery, or even act as drug by themselves. Conclusion: Various types of SAPs have been designed and used for drug delivery following various strategies, suggesting that SAPs as a category of versatile nanomaterials have promising potential in the field of nanomedicine.

Peptide self-assembly for nanomaterials: the old new kid on the block

2015 ◽  
Vol 44 (22) ◽  
pp. 8288-8300 ◽  
Author(s):  
Emiliana De Santis ◽  
Maxim G. Ryadnov
Keyword(s):  
Self Assembly ◽  
Self Assembling ◽  
Peptide Materials

Self-assembling peptide materials are categorised according to main nanomaterial forms in relation to non-peptide materials.

scholarly journals Self-Assembling Multifunctional Peptide Dimers for Gene Delivery Systems

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Kitae Ryu ◽  
Gyeong Jin Lee ◽  
Ji-yeong Choi ◽  
Taewan Kim ◽  
Tae-il Kim
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Weight Ratio ◽  
Delivery Systems ◽  
C2c12 Cells ◽  
Endosomal Escape ◽  
Hek293 Cells ◽  
Matrix Metalloproteinase 2 ◽  
Self Assembling ◽  
Hydrophobic Moiety

Self-assembling multifunctional peptide was designed for gene delivery systems. The multifunctional peptide (MP) consists of cellular penetrating peptide moiety (R8), matrix metalloproteinase-2 (MMP-2) specific sequence (GPLGV), pH-responsive moiety (H5), and hydrophobic moiety (palmitic acid) (CR8GPLGVH5-Pal). MP was oxidized to form multifunctional peptide dimer (MPD) by DMSO oxidation of thiols in terminal cysteine residues. MPD could condense pDNA successfully at a weight ratio of 5. MPD itself could self-assemble into submicron micelle particles via hydrophobic interaction, of which critical micelle concentration is about 0.01 mM. MPD showed concentration-dependent but low cytotoxicity in comparison with PEI25k. MPD polyplexes showed low transfection efficiency in HEK293 cells expressing low level of MMP-2 but high transfection efficiency in A549 and C2C12 cells expressing high level of MMP-2, meaning the enhanced transfection efficiency probably due to MMP-induced structural change of polyplexes. Bafilomycin A1-treated transfection results suggest that the transfection of MPD is mediated via endosomal escape by endosome buffering ability. These results show the potential of MPD for MMP-2 targeted gene delivery systems due to its multifunctionality.

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