| 1. |
- Aili, Daniel, et al.
(author)
-
Bioresponsive peptide-inorganic hybrid nanomaterials
- 2010
-
In: Chemical Society Reviews. - : Royal Society of Chemistry. - 0306-0012 .- 1460-4744. ; 39:9, s. 3358-3370
-
Research review (peer-reviewed)abstract
- Bioanalytical techniques that enable simple, fast and reliable high sensitivity monitoring of biomolecular interactions are of immense importance for diagnostics and drug development. This tutorial review provides an overview of recent progress in the development of peptide-based hybrid nanomaterials that transduce molecular interactions by exploiting the optical and magnetic properties of nanoparticles. Peptides have emerged as an interesting alternative to conventional biomolecular receptors, such as antibodies, and are facilitating the design of responsive hybrid nanomaterials that are both robust and sensitive for biodiagnostic applications.
|
|
| 2. |
- Aili, Daniel, et al.
(author)
-
Hybrid Nanoparticle-Liposome Detection of Phospholipase Activity
- 2011
-
In: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 11:4, s. 1401-1405
-
Journal article (peer-reviewed)abstract
- A flexible nanoparticle-based phospholipase (PL) assay is demonstrated in which the enzymatic substrate is decoupled from the nanoparticle surface. Liposomes are loaded with a polypeptide that is designed to heteroassociate with a second polypeptide immobilized on gold nanoparticies. Release of this polypeptide from the liposornes, triggered by PL, induces a folding-dependent nanoparticle bridging aggregation. The colorimetric response from this aggregation enables straightforward and continuous detection of PL in the picomolar range. The speed, specificity, and flexibility of this assay make it appropriate for a range of applications, from point of care diagnostics to high throughput pharmaceutical screening.
|
|
| 3. |
- Aili, Daniel, 1977-
(author)
-
Polypeptide-Based Nanoscale Materials
- 2008
-
Doctoral thesis (other academic/artistic)abstract
- Self-assembly has emerged as a promising technique for fabrication of novel hybrid materials and nanostructures. The work presented in this thesis has been focused on developing nanoscale materials based on synthetic de novo designed polypeptides. The polypeptides have been utilized for the assembly of gold nanoparticles, fibrous nanostructures, and for sensing applications.The 42-residue polypeptides are designed to fold into helix-loop-helix motifs and dimerize to form four-helix bundles. Folding is primarily driven by the formation of a hydrophobic core made up by the hydrophobic faces of the amphiphilic helices. The peptides have either a negative or positive net charge at neutral pH, depending on the relative abundance of Glu and Lys. Charge repulsion thus prevents homodimerization at pH 7 while promoting hetero-dimerization through the formation of stabilising salt bridges. A Cys incorporated in position 22, located in the loop region, allowed for directed, thiol-dependent, immobilization on planar gold surfaces and gold nanoparticles. The negatively charged (Glu-rich) peptide formed homodimers and folded in solution at pH < 6 or in the presence of certain metal ions, such as Zn2+. The folding properties of this peptide were retained when immobilized directly on gold, which enabled reversible assembly of gold nanoparticles resulting in aggregates with well-defined interparticle separations. Particle aggregation was found to induce folding of the immobilized peptides but folding could also be utilized to induce aggregation of the particles by exploiting the highly specific interactions involved in both homodimerization and hetero-association. The possibility to control the assembly of polypeptide-functionalized gold nanoparticles was utilized in a colorimetric protein assay. Analyte binding to immobilized ligands prevented the formation of dense particle aggregates when subjecting the particles to conditions normally causing extensive aggregation. Analyte binding could hence easily be distinguished by the naked eye. Moreover, the peptides were utilized to assemble gold nanoparticles on planar gold and silica substrates.Fibrous nanostructures were realized by linking monomers through a disulphide-bridge. The disulphide-linked peptides were found to spontaneously assemble into long and extremely thin peptide fibres as a result of a propagating association mediated by folding into four-helix bundles.
|
|
| 4. |
- Aili, Daniel, et al.
(author)
-
Polypeptide Folding-Mediated Tuning of the Optical and Structural Properties of Gold Nanoparticle Assemblies
- 2011
-
In: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 11:12, s. 5564-5573
-
Journal article (peer-reviewed)abstract
- Responsive hybrid nanomaterials with well-defined properties are of significant interest for the development of biosensors with additional applications in tissue engineering and drug delivery. Here, we present a detailed characterization using UV-vis spectroscopy and small angle X-ray scattering of a hybrid material comprised of polypeptide-decorated gold nanoparticles with highly controllable assembly properties. The assembly is triggered by a folding-dependent bridging of the particles mediated by the heteroassociation of immobilized helix-loop-helix polypeptides and a complementary nonlinear polypeptide present in solution. The polypeptides are de novo designed to associate and fold into a heterotrimeric complex comprised of two disulfide-linked four-helix bundles. The particles form structured assemblies with a highly defined interparticle gap (4.8 +/- 0.4 nm) that correlates to the size of the folded polypeptides. Transitions in particle aggregation dynamics, mass-fractal dimensions and ordering, as a function of particle size and the concentration of the bridging polypeptide, are observed; these have significant effects on the optical properties of the assemblies. The assembly and ordering of the particles are highly complex processes that are affected by a large number of variables including the number of polypeptides bridging the particles and the particle mobility within the aggregates. A fundamental understanding of these processes is of paramount interest for the development of novel hybrid nanomaterials with tunable structural and optical properties and for the optimization of nanoparticle-based colorimetric biodetection strategies.
|
|
| 5. |
- Barriga, Hanna M. G., et al.
(author)
-
Coupling Lipid Nanoparticle Structure and Automated Single-Particle Composition Analysis to Design Phospholipase-Responsive Nanocarriers
- 2022
-
In: Advanced Materials. - : Wiley. - 0935-9648 .- 1521-4095. ; 34:26
-
Journal article (peer-reviewed)abstract
- Lipid nanoparticles (LNPs) are versatile structures with tunable physicochemical properties that are ideally suited as a platform for vaccine delivery and RNA therapeutics. A key barrier to LNP rational design is the inability to relate composition and structure to intracellular processing and function. Here Single Particle Automated Raman Trapping Analysis (SPARTA) is combined with small-angle X-ray and neutron scattering (SAXS/SANS) techniques to link LNP composition with internal structure and morphology and to monitor dynamic LNP-phospholipase D (PLD) interactions. This analysis demonstrates that PLD, a key intracellular trafficking mediator, can access the entire LNP lipid membrane to generate stable, anionic LNPs. PLD activity on vesicles with matched amounts of enzyme substrate is an order of magnitude lower, indicating that the LNP lipid membrane structure can be used to control enzyme interactions. This represents an opportunity to design enzyme-responsive LNP solutions for stimuli-responsive delivery and diseases where PLD is dysregulated.
|
|
| 6. |
- Bost, Jeremy P., et al.
(author)
-
Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides
- 2022
-
In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
-
Journal article (peer-reviewed)abstract
- The therapeutic and research potentials of oligonucleotides (ONs) have been hampered in part by their inability to effectively escape endosomal compartments to reach their cytosolic and nuclear targets. Splice-switching ONs (SSOs) can be used with endosomolytic small molecule compounds to increase functional delivery. So far, development of these compounds has been hindered by a lack of high-resolution methods that can correlate SSO trafficking with SSO activity. Here we present in-depth characterization of two novel endosomolytic compounds by using a combination of microscopic and functional assays with high spatiotemporal resolution. This system allows the visualization of SSO trafficking, evaluation of endosomal membrane rupture, and quantitates SSO functional activity on a protein level in the presence of endosomolytic compounds. We confirm that the leakage of SSO into the cytosol occurs in parallel with the physical engorgement of LAMP1-positive late endosomes and lysosomes. We conclude that the new compounds interfere with SSO trafficking to the LAMP1-positive endosomal compartments while inducing endosomal membrane rupture and concurrent ON escape into the cytosol. The efficacy of these compounds advocates their use as novel, potent, and quick-acting transfection reagents for antisense ONs.
|
|
| 7. |
- Datta-Chaudhuri, Timir, et al.
(author)
-
The Fourth Bioelectronic Medicine Summit "Technology Targeting Molecular Mechanisms" : current progress, challenges, and charting the future
- 2021
-
In: Bioelectronic medicine. - : BioMed Central. - 2332-8886. ; 7:1
-
Journal article (other academic/artistic)abstract
- There is a broad and growing interest in Bioelectronic Medicine, a dynamic field that continues to generate new approaches in disease treatment. The fourth bioelectronic medicine summit "Technology targeting molecular mechanisms" took place on September 23 and 24, 2020. This virtual meeting was hosted by the Feinstein Institutes for Medical Research, Northwell Health. The summit called international attention to Bioelectronic Medicine as a platform for new developments in science, technology, and healthcare. The meeting was an arena for exchanging new ideas and seeding potential collaborations involving teams in academia and industry. The summit provided a forum for leaders in the field to discuss current progress, challenges, and future developments in Bioelectronic Medicine. The main topics discussed at the summit are outlined here.
|
|
| 8. |
- de la Rica, Roberto, et al.
(author)
-
Enzyme-responsive nanoparticles for drug release and diagnostics
- 2012
-
In: Advanced Drug Delivery Reviews. - : Elsevier. - 0169-409X .- 1872-8294. ; 64:11, s. 967-978
-
Research review (peer-reviewed)abstract
- Enzymes are key components of the bionanotechnology toolbox that possess exceptional biorecognition capabilities and outstanding catalytic properties. When combined with the unique physical properties of nanomaterials, the resulting enzyme-responsive nanoparticles can be designed to perform functions efficiently and with high specificity for the triggering stimulus. This powerful concept has been successfully applied to the fabrication of drug delivery schemes where the tissue of interest is targeted via release of cargo triggered by the biocatalytic action of an enzyme. Moreover, the chemical transformation of the carrier by the enzyme can also generate therapeutic molecules, therefore paving the way to design multimodal nanomedicines with synergistic effects. Dysregulation of enzymatic activity has been observed in a number of severe pathological conditions, and this observation is useful not only to program drug delivery in vivo but also to fabricate ultrasensitive sensors for diagnosing these diseases. In this review, several enzyme-responsive nanomaterials such as polymer-based nanoparticles, liposomes, gold nanoparticles and quantum dots are introduced, and the modulation of their physicochemical properties by enzymatic activity emphasized. When known, toxicological issues related to the utilization nanomaterials are highlighted. Key examples of enzyme-responsive nanomaterials for drug delivery and diagnostics are presented, classified by the type of effector biomolecule, including hydrolases such as proteases, lipases and glycosidases, and oxidoreductases.
|
|
| 9. |
- Gormley, Adam J., et al.
(author)
-
Layer-by-Layer Self-Assembly of Polymer Films and Capsules through Coiled-Coil Peptides
- 2015
-
In: Chemistry of Materials. - : AMER CHEMICAL SOC. - 0897-4756 .- 1520-5002. ; 27:16, s. 5820-5824
-
Journal article (peer-reviewed)abstract
- The layer-by-layer (LbL) technique is a simple and robust process for fabricating functional multilayer thin films. Here, we report the use of de novo designed polypeptides that self-assemble into coiled-coil structures (four-helix bundles) as a driving force for specific multilayer assembly. These pH- (sensitive between pH 4 and 7) and enzyme-responsive polypeptides were conjugated to polymers, and the LbL assembly of the polymer-peptide conjugates allowed the deposition of up to four polymer-peptide layers on planar surfaces and colloidal substrates. Stable hollow capsules were obtained, and by taking advantage of the peptides susceptibility to specific enzymatic cleavage, release of encapsulated cargo within the carriers can be triggered within 2 h in the presence of matrix metalloproteinase-7. The enormous diversity of materials that can form highly controllable and programmable coiled-coil interactions creates new opportunities and allows further exploration of the multilayer assembly and the formation of carrier capsules with unique functional properties.
|
|
| 10. |
- Guex, Anne Geraldine, et al.
(author)
-
Highly porous scaffolds of PEDOT:PSS for bone tissue engineering
- 2017
-
In: Acta Biomaterialia. - : ELSEVIER SCI LTD. - 1742-7061 .- 1878-7568. ; 62, s. 91-101
-
Journal article (peer-reviewed)abstract
- Conjugated polymers have been increasingly considered for the design of conductive materials in the field of regenerative medicine. However, optimal scaffold properties addressing the complexity of the desired tissue still need to be developed. The focus of this study lies in the development and evaluation of a conductive scaffold for bone tissue engineering. In this study PEDOT:PSS scaffolds were designed and evaluated in vitro using MC3T3-E1 osteogenic precursor cells, and the cells were assessed for distinct differentiation stages and the expression of an osteogenic phenotype. Ice-templated PEDOT:PSS scaffolds presented high pore interconnectivity with a median pore diameter of 53.6 +/- 5.9 mu m and a total pore surface area of 7.72 +/- 1.7 m(2).g(-1). The electrical conductivity, based on I-V curves, was measured to be 140 mu S.cm(-1) with a reduced, but stable conductivity of 6.1 mu S.cm(-1) after 28 days in cell culture media. MC3T3-E1 gene expression levels of ALPL, COL1A1 and RUNX2 were significantly enhanced after 4 weeks, in line with increased extracellular matrix mineralisation, and osteocalcin deposition. These results demonstrate that a porous material, based purely on PEDOT:PSS, is suitable as a scaffold for bone tissue engineering and thus represents a promising candidate for regenerative medicine. Statement of Significance Tissue engineering approaches have been increasingly considered for the repair of non-union fractions, craniofacial reconstruction or large bone defect replacements. The design of complex biomaterials and successful engineering of 3-dimensional tissue constructs is of paramount importance to meet this clinical need. Conductive scaffolds, based on conjugated polymers, present interesting candidates to address the piezoelectric properties of bone tissue and to induce enhanced osteogenesis upon implantation. However, conductive scaffolds have not been investigated in vitro in great measure. To this end, we have developed a highly porous, electrically conductive scaffold based on PEDOT:PSS, and provide evidence that this purely synthetic material is a promising candidate for bone tissue engineering. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd.
|
|
