In resource-constrained countries, affordable methodologies for the detection of disease biomarkers at ultralow concentrations can potentially improve the standard of living. However, current ...strategies for ultrasensitive detection often require sophisticated instruments that may not be available in laboratories with fewer resources. Here, we circumvent this problem by introducing a signal generation mechanism for biosensing that enables the detection of a few molecules of analyte with the naked eye. The enzyme label of an enzyme-linked immunosorbent assay (ELISA) controls the growth of gold nanoparticles and generates coloured solutions with distinct tonality when the analyte is present. Prostate specific antigen (PSA) and HIV-1 capsid antigen p24 were detected in whole serum at the ultralow concentration of 1 × 10(-18) g ml(-1). p24 was also detected with the naked eye in the sera of HIV-infected patients showing viral loads undetectable by a gold standard nucleic acid-based test.
The application of nanomaterials to detect disease biomarkers is giving rise to ultrasensitive assays, with scientists exploiting the many advantageous physical and chemical properties of ...nanomaterials. The fundamental basis of such work is to link unique phenomena that arise at the nanoscale to the presence of a specific analyte biomolecule, and to modulate the intensity of such phenomena in a ratiometric fashion, in direct proportion with analyte concentration. Precise engineering of nanomaterial surfaces is of utmost importance here, as the interface between the material and the biological environment is where the key interactions occur. In this tutorial review, we discuss the use of plasmonic nanomaterials in the development of biodiagnostic tools for the detection of a large variety of biomolecular analytes, and how their plasmonic properties give rise to tunable optical characteristics and surface enhanced Raman signals. We put particular focus on studies that have explored the efficacy of the systems using physiological samples in an effort to highlight the clinical potential of such assays.
Peptide- and protein-nanoparticle conjugates have emerged as powerful tools for biomedical applications, enabling the treatment, diagnosis, and prevention of disease. In this review, we focus on the ...key roles played by peptides and proteins in improving, controlling, and defining the performance of nanotechnologies. Within this framework, we provide a comprehensive overview of the key sequences and structures utilised to provide biological and physical stability to nano-constructs, direct particles to their target and influence their cellular and tissue distribution, induce and control biological responses, and form polypeptide self-assembled nanoparticles. In doing so, we highlight the great advances made by the field, as well as the challenges still faced in achieving the clinical translation of peptide- and protein-functionalised nano-drug delivery vehicles, imaging species, and active therapeutics.
Colloidal nanoparticles as advanced biological sensors Howes, Philip D.; Chandrawati, Rona; Stevens, Molly M.
Science (American Association for the Advancement of Science),
10/2014, Volume:
346, Issue:
6205
Journal Article
Peer reviewed
Open access
Biological sensing using nanoparticles
Colloidal fluorescent and plasmonic nanoparticles yield intense responses to incident light, making them useful as sensors or probes for sensitive detection in ...solution. Howes
et al.
review the potential uses of nanoparticle biosensors in research and diagnostics. A range of methods allow for the chemical modification of the particle surfaces so that they can be tuned for specific analytes and give optical signals for a range of biological conditions of interest. Signals can be detected in complex media or in vivo making the particles of interest for both laboratory research and in clinical settings.
Science
, this issue
10.1126/science.1247390
Colloidal nanoparticle biosensors have received intense scientific attention and offer promising applications in both research and medicine. We review the state of the art in nanoparticle development, surface chemistry, and biosensing mechanisms, discussing how a range of technologies are contributing toward commercial and clinical translation. Recent examples of success include the ultrasensitive detection of cancer biomarkers in human serum and in vivo sensing of methyl mercury. We identify five key materials challenges, including the development of robust mass-scale nanoparticle synthesis methods, and five broader challenges, including the use of simulations and bioinformatics-driven experimental approaches for predictive modeling of biosensor performance. The resultant generation of nanoparticle biosensors will form the basis of high-performance analytical assays, effective multiplexed intracellular sensors, and sophisticated in vivo probes.
Cubosomes are highly stable nanoparticles formed from the lipid cubic phase and stabilized by a polymer based outer corona. Bicontinuous lipid cubic phases consist of a single lipid bilayer that ...forms a continuous periodic membrane lattice structure with pores formed by two interwoven water channels. Cubosome composition can be tuned to engineer pore sizes or include bioactive lipids, the polymer outer corona can be used for targeting and they are highly stable under physiological conditions. Compared to liposomes, the structure provides a significantly higher membrane surface area for loading of membrane proteins and small drug molecules. Owing to recent advances, they can be engineered in vitro in both bulk and nanoparticle formats with applications including drug delivery, membrane bioreactors, artificial cells, and biosensors. This review outlines recent advances in cubosome technology enabling their application and provides guidelines for the rational design of new systems for biomedical applications.
Cubosomes are nanoparticles with an internal periodic lipid membrane separated by two distinct water channels. The surface is stabilized by a polymer outer corona. Recent advances have enabled the rational design of cubosome systems. Key considerations are outlined for engineering cubosomes for tailor‐made applications including delivery, biosensing, and medical applications.
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.
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The components of bone assemble hierarchically to provide stiffness and toughness. However, the organization and relationship between bone's principal components-mineral and collagen-has not been ...clearly elucidated. Using three-dimensional electron tomography imaging and high-resolution two-dimensional electron microscopy, we demonstrate that bone mineral is hierarchically assembled beginning at the nanoscale: Needle-shaped mineral units merge laterally to form platelets, and these are further organized into stacks of roughly parallel platelets. These stacks coalesce into aggregates that exceed the lateral dimensions of the collagen fibrils and span adjacent fibrils as continuous, cross-fibrillar mineralization. On the basis of these observations, we present a structural model of hierarchy and continuity for the mineral phase, which contributes to the structural integrity of bone.
The conjugation of biomolecules can impart materials with the bioactivity necessary to modulate specific cell behaviors. While the biological roles of particular polypeptide, oligonucleotide, and ...glycan structures have been extensively reviewed, along with the influence of attachment on material structure and function, the key role played by the conjugation strategy in determining activity is often overlooked. In this review, we focus on the chemistry of biomolecule conjugation and provide a comprehensive overview of the key strategies for achieving controlled biomaterial functionalization. No universal method exists to provide optimal attachment, and here we will discuss both the relative advantages and disadvantages of each technique. In doing so, we highlight the importance of carefully considering the impact and suitability of a particular technique during biomaterial design.
Hydrogels are one of the most commonly explored classes of biomaterials. Their chemical and structural versatility has enabled their use across a wide range of applications, including tissue ...engineering, drug delivery, and cell culture. Hydrogels form upon a sol–gel transition, which can be elicited by different triggers designed to enable precise control over hydrogelation kinetics and hydrogel structure. The chosen hydrogelation trigger and chemistry can have a profound effect on the success of the targeted application. In this Progress Report, a critical overview of recent advances in hydrogel design is presented, with a focus on the available strategies used to trigger the formation of hydrogel networks (e.g., temperature, light, ultrasound). These triggers are presented within a new classification system, and their suitability for six key hydrogel‐based applications is assessed. This Progress Report is intended to guide trigger selection for new hydrogel applications and inspire the rational design of new hydrogelation trigger mechanisms.
This Progress Report provides a critical overview of recent advances in hydrogel design, and focuses on the currently available approaches to trigger hydrogelation (e.g., temperature, pH, enzymes, light, ultrasound). These triggers are presented within a new classification system and illustrated with key examples and applications. Future opportunities are outlined to aid trigger selection and inspire the next generation of gelation mechanisms.
Extracellular vesicles (EVs) are phospholipid-based particles endogenously produced by cells. Their natural composition and selective cell interactions make them promising drug carriers. However, in ...order to harness their properties, efficient exogenous drug encapsulation methods need to be investigated. Here, EVs from various cellular origins (endothelial, cancer and stem cells) were produced and characterised for size and composition. Porphyrins of different hydrophobicities were employed as model drugs and encapsulated into EVs using various passive and active methods (electroporation, saponin, extrusion and dialysis). Hydrophobic compounds loaded very efficiently into EVs and at significantly higher amounts than into standard liposomes composed of phosphocholine and cholesterol using passive incubation. Moreover, loading into EVs significantly increased the cellular uptake by >60% and the photodynamic effect of hydrophobic porphyrins in vitro compared to free or liposome encapsulated drug. The active encapsulation techniques, with the saponin-assisted method in particular, allowed an up to 11 fold higher drug loading of hydrophilic porphyrins compared to passive methods. EVs loaded with hydrophilic porphyrins induced a stronger phototoxic effect than free drug in a cancer cell model. Our findings create a firm basis for the development of EVs as smart drug carriers based on straightforward and transferable methods.
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