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Functional Peptide-Based Nanomaterials

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Bioorganic Chemistry".

Deadline for manuscript submissions: closed (1 June 2020) | Viewed by 31080

Special Issue Editor


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Guest Editor
Pritzker School of Molecular Engineering, The University of Chicago, 5640 S. Ellis Avenue, Chicago, IL 60637, USA
Interests: biomaterials; peptides; self-assembly; molecular engineering; bioengineering; nanomaterials; bioinspired materials; nanomedicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Peptides are intrinsically functional systems through a variety of interactions provided by the side chains of the amino acids. Synthetic amino acids enable addition of noncanonical functionalities in addition to the natural reactions. Peptides can also self-assemble into nanostructures and produce nanoscale materials that can be exploited as extracellular matrix mimics, protein function and drug delivery applications. Recently, peptide-based materials have been showed to be convenient for manipulating biological machinery and engineering biological systems.  

This Special Issue covers a variety of peptide based functional nanomaterials, which can find applications in regenerative medicine, drug delivery, bioimaging, immunoengineering, and biocatalysis. Review and research articles in this Special Issue will provide insights and perspectives in applications of various peptide-based nanomaterials.

Prof. Mustafa O. Guler
Guest Editor

Manuscript Submission Information

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Keywords

  • Peptides
  • Nanomaterials
  • Stimuli-responsive systems
  • Biomimetics
  • Bioinspired materials
  • Nanomedicine
  • Stimuli-responsive

Published Papers (7 papers)

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Research

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15 pages, 1922 KiB  
Article
Stable Formulations of Peptide-Based Nanogels
by Elisabetta Rosa, Carlo Diaferia, Enrico Gallo, Giancarlo Morelli and Antonella Accardo
Molecules 2020, 25(15), 3455; https://doi.org/10.3390/molecules25153455 - 29 Jul 2020
Cited by 17 | Viewed by 3745
Abstract
Recently, nanogels have been identified as innovative formulations for enlarging the application of hydrogels (HGs) in the area of drug delivery or in diagnostic imaging. Nanogels are HGs-based aggregates with sizes in the range of nanometers and formulated in order to obtain injectable [...] Read more.
Recently, nanogels have been identified as innovative formulations for enlarging the application of hydrogels (HGs) in the area of drug delivery or in diagnostic imaging. Nanogels are HGs-based aggregates with sizes in the range of nanometers and formulated in order to obtain injectable preparations. Regardless of the advantages offered by peptides in a hydrogel preparation, until now, only a few examples of peptide-based nanogels (PBNs) have been developed. Here, we describe the preparation of stable PBNs based on Fmoc-Phe-Phe-OH using three different methods, namely water/oil emulsion (W/O), top-down, and nanogelling in water. The effect of the hydrophilic–lipophilic balance (HLB) in the formulation was also evaluated in terms of size and stability. The resulting nanogels were found to encapsulate the anticancer drug doxorubicin, chosen as the model drug, with a drug loading comparable with those of the liposomes. Full article
(This article belongs to the Special Issue Functional Peptide-Based Nanomaterials)
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24 pages, 6836 KiB  
Article
Preclinical Evaluation of NHS-Activated Gold Nanoparticles Functionalized with Bombesin or Neurotensin-Like Peptides for Targeting Colon and Prostate Tumours
by Livia Elena Chilug, Dana Niculae, Radu Anton Leonte, Alexandrina Nan, Rodica Turcu, Cosmin Mustaciosu, Radu Marian Serban, Vasile Lavric and Gina Manda
Molecules 2020, 25(15), 3363; https://doi.org/10.3390/molecules25153363 - 24 Jul 2020
Cited by 9 | Viewed by 3407
Abstract
Recent advances and large-scale use of hybrid imaging modalities like PET-CT have led to the necessity of improving nano-drug carriers that can facilitate both functional and metabolic screening in nuclear medicine applications. In this study, we focused on the evaluation of four potential [...] Read more.
Recent advances and large-scale use of hybrid imaging modalities like PET-CT have led to the necessity of improving nano-drug carriers that can facilitate both functional and metabolic screening in nuclear medicine applications. In this study, we focused on the evaluation of four potential imaging nanoparticle structures labelled with the 68Ga positron emitter. For this purpose, we functionalized NHS-activated PEG-gold nanoparticles with 68Ga-DOTA-Neuromedin B, 68Ga-DOTA-PEG(4)-BBN(7-14), 68Ga-DOTA-NT and 68Ga-DOTA-Neuromedin N. In vitro binding kinetics and specific binding to human HT-29 colon carcinoma cells and DU-145 prostate carcinoma cells respectively were assessed, over 75% retention being obtained in the case of 68Ga-DOTA-PEG(4)-BBN(7-14)-AuNP in prostate tumour cells and over 50% in colon carcinoma cells. Biodistribution in NU/J mice highlighted a three-fold uptake increase in tumours at 30 min post-injection of 68Ga-DOTA-NT-AuNP and 68Ga-DOTA-PEG(4)-BBN(7-14)-AuNP compared to 68Ga-DOTA-NT and 68Ga-DOTA-PEG(4)-BBN(7-14) respectively, therewith fast distribution in prostate and colon tumours and minimum accumulation in non-targeted tissues. Full article
(This article belongs to the Special Issue Functional Peptide-Based Nanomaterials)
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10 pages, 2110 KiB  
Article
Biocatalysis of d,l-Peptide Nanofibrillar Hydrogel
by Tiziano Carlomagno, Maria C. Cringoli, Slavko Kralj, Marina Kurbasic, Paolo Fornasiero, Paolo Pengo and Silvia Marchesan
Molecules 2020, 25(13), 2995; https://doi.org/10.3390/molecules25132995 - 30 Jun 2020
Cited by 14 | Viewed by 3606
Abstract
Self-assembling peptides are attracting wide interest as biodegradable building blocks to achieve functional nanomaterials that do not persist in the environment. Amongst the many applications, biocatalysis is gaining momentum, although a clear structure-to-activity relationship is still lacking. This work applied emerging design rules [...] Read more.
Self-assembling peptides are attracting wide interest as biodegradable building blocks to achieve functional nanomaterials that do not persist in the environment. Amongst the many applications, biocatalysis is gaining momentum, although a clear structure-to-activity relationship is still lacking. This work applied emerging design rules to the heterochiral octapeptide sequence His–Leu–DLeu–Ile–His–Leu–DLeu–Ile for self-assembly into nanofibrils that, at higher concentration, give rise to a supramolecular hydrogel for the mimicry of esterase-like activity. The peptide was synthesized by solid-phase and purified by HPLC, while its identity was confirmed by 1H-NMR and electrospray ionization (ESI)-MS. The hydrogel formed by this peptide was studied with oscillatory rheometry, and the supramolecular behavior of the peptide was investigated with transmission electron microscopy (TEM) analysis, circular dichroism (CD) spectroscopy, thioflavin T amyloid fluorescence assay, and attenuated total reflectance (ATR) Fourier-transform infrared (FT-IR) spectroscopy. The biocatalytic activity was studied by monitoring the hydrolysis of p-nitrophenyl acetate (pNPA) at neutral pH, and the reaction kinetics followed an apparent Michaelis–Menten model, for which a Lineweaver–Burk plot was produced to determine its enzymatic parameters for a comparison with the literature. Finally, LC–MS analysis was conducted on a series of experiments to evaluate the extent of, if any, undesired peptide acetylation at the N-terminus. In conclusion, we provide new insights that allow gaining a clearer picture of self-assembling peptide design rules for biocatalysis. Full article
(This article belongs to the Special Issue Functional Peptide-Based Nanomaterials)
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13 pages, 4607 KiB  
Article
Preparation of Protein–Peptide–Calcium Phosphate Composites for Controlled Protein Release
by Katsuya Kato, Sungho Lee and Fukue Nagata
Molecules 2020, 25(10), 2312; https://doi.org/10.3390/molecules25102312 - 14 May 2020
Cited by 4 | Viewed by 2542
Abstract
Protein–peptide–calcium phosphate composites were developed for achieving sustainable and controlled protein release. Bovine serum albumin (BSA) as a model acidic protein was efficiently encapsulated with basic polypeptides such as polylysine and polyarginine during the precipitation of calcium phosphate (CaP). The prepared composites were [...] Read more.
Protein–peptide–calcium phosphate composites were developed for achieving sustainable and controlled protein release. Bovine serum albumin (BSA) as a model acidic protein was efficiently encapsulated with basic polypeptides such as polylysine and polyarginine during the precipitation of calcium phosphate (CaP). The prepared composites were fully characterized in terms of their morphologies, crystallinities, and the porosity of their structures, and from these analyses, it was observed that there are no significant differences between the composites. Scanning transmission electron microscopy and energy dispersive X-ray spectroscopy analysis indicated a homogeneous distribution of nitrogen and sulfur, confirming the uniform distribution of BSA and polypeptide in the CaP composite. In vitro release studies demonstrated that the composite prepared with the peptides α-polylysine and polyarginine were suitable for the gradual release of the protein BSA, while those containing ε-polylysine and no peptide were unsuitable for protein release. Additionally, these composites showed high hemocompatibility for mouse red blood cells, and the osteoblast-like cell proliferation and spread in media with the composites prepared using BSA and α-polylysine showed similar tendencies to medium with no composite. From these results, protein–peptide–CaP composites are expected to be useful as highly biocompatible protein delivery agents. Full article
(This article belongs to the Special Issue Functional Peptide-Based Nanomaterials)
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12 pages, 2464 KiB  
Article
Targeted Dendrimer-Coated Magnetic Nanoparticles for Selective Delivery of Therapeutics in Living Cells
by Paola Parlanti, Adriano Boni, Giovanni Signore and Melissa Santi
Molecules 2020, 25(9), 2252; https://doi.org/10.3390/molecules25092252 - 10 May 2020
Cited by 15 | Viewed by 3127
Abstract
Nanoparticles are widely used as theranostic agents for the treatment of various pathologies, including cancer. Among all, dendrimers-based nanoparticles represent a valid approach for drugs delivery, thanks to their controllable size and surface properties. Indeed, dendrimers can be easily loaded with different payloads [...] Read more.
Nanoparticles are widely used as theranostic agents for the treatment of various pathologies, including cancer. Among all, dendrimers-based nanoparticles represent a valid approach for drugs delivery, thanks to their controllable size and surface properties. Indeed, dendrimers can be easily loaded with different payloads and functionalized with targeting agents. Moreover, they can be used in combination with other materials such as metal nanoparticles for combinatorial therapies. Here, we present the formulation of an innovative nanostructured hybrid system composed by a metallic core and a dendrimers-based coating that is able to deliver doxorubicin specifically to cancer cells through a targeting agent. Its dual nature allows us to transport nanoparticles to our site of interest through the magnetic field and specifically increase internalization by exploiting the T7 targeting peptide. Our system can release the drug in a controlled pH-dependent way, causing more than 50% of cell death in a pancreatic cancer cell line. Finally, we show how the system was internalized inside cancer cells, highlighting a peculiar disassembly of the nanostructure at the cell surface. Indeed, only the dendrimeric portion is internalized, while the metal core remains outside. Thanks to these features, our nanosystem can be exploited for a multistage magnetic vector. Full article
(This article belongs to the Special Issue Functional Peptide-Based Nanomaterials)
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Review

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37 pages, 14818 KiB  
Review
Peptide-Based Nanoassemblies in Gene Therapy and Diagnosis: Paving the Way for Clinical Application
by Shabnam Tarvirdipour, Xinan Huang, Voichita Mihali, Cora-Ann Schoenenberger and Cornelia G. Palivan
Molecules 2020, 25(15), 3482; https://doi.org/10.3390/molecules25153482 - 31 Jul 2020
Cited by 36 | Viewed by 7245
Abstract
Nanotechnology approaches play an important role in developing novel and efficient carriers for biomedical applications. Peptides are particularly appealing to generate such nanocarriers because they can be rationally designed to serve as building blocks for self-assembling nanoscale structures with great potential as therapeutic [...] Read more.
Nanotechnology approaches play an important role in developing novel and efficient carriers for biomedical applications. Peptides are particularly appealing to generate such nanocarriers because they can be rationally designed to serve as building blocks for self-assembling nanoscale structures with great potential as therapeutic or diagnostic delivery vehicles. In this review, we describe peptide-based nanoassemblies and highlight features that make them particularly attractive for the delivery of nucleic acids to host cells or improve the specificity and sensitivity of probes in diagnostic imaging. We outline the current state in the design of peptides and peptide-conjugates and the paradigms of their self-assembly into well-defined nanostructures, as well as the co-assembly of nucleic acids to form less structured nanoparticles. Various recent examples of engineered peptides and peptide-conjugates promoting self-assembly and providing the structures with wanted functionalities are presented. The advantages of peptides are not only their biocompatibility and biodegradability, but the possibility of sheer limitless combinations and modifications of amino acid residues to induce the assembly of modular, multiplexed delivery systems. Moreover, functions that nature encoded in peptides, such as their ability to target molecular recognition sites, can be emulated repeatedly in nanoassemblies. Finally, we present recent examples where self-assembled peptide-based assemblies with “smart” activity are used in vivo. Gene delivery and diagnostic imaging in mouse tumor models exemplify the great potential of peptide nanoassemblies for future clinical applications. Full article
(This article belongs to the Special Issue Functional Peptide-Based Nanomaterials)
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33 pages, 7611 KiB  
Review
Supramolecular Peptide Assemblies as Antimicrobial Scaffolds
by Andrew W. Simonson, Matthew R. Aronson and Scott H. Medina
Molecules 2020, 25(12), 2751; https://doi.org/10.3390/molecules25122751 - 14 Jun 2020
Cited by 26 | Viewed by 6604
Abstract
Antimicrobial discovery in the age of antibiotic resistance has demanded the prioritization of non-conventional therapies that act on new targets or employ novel mechanisms. Among these, supramolecular antimicrobial peptide assemblies have emerged as attractive therapeutic platforms, operating as both the bactericidal agent and [...] Read more.
Antimicrobial discovery in the age of antibiotic resistance has demanded the prioritization of non-conventional therapies that act on new targets or employ novel mechanisms. Among these, supramolecular antimicrobial peptide assemblies have emerged as attractive therapeutic platforms, operating as both the bactericidal agent and delivery vector for combinatorial antibiotics. Leveraging their programmable inter- and intra-molecular interactions, peptides can be engineered to form higher ordered monolithic or co-assembled structures, including nano-fibers, -nets, and -tubes, where their unique bifunctionalities often emerge from the supramolecular state. Further advancements have included the formation of macroscopic hydrogels that act as bioresponsive, bactericidal materials. This systematic review covers recent advances in the development of supramolecular antimicrobial peptide technologies and discusses their potential impact on future drug discovery efforts. Full article
(This article belongs to the Special Issue Functional Peptide-Based Nanomaterials)
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