RESUMO
Tools capable of imaging and perturbing mechanical signaling pathways with fine spatiotemporal resolution have been elusive, despite their importance in diverse cellular processes. The challenge in developing a mechanogenetic toolkit (i.e., selective and quantitative activation of genetically encoded mechanoreceptors) stems from the fact that many mechanically activated processes are localized in space and time yet additionally require mechanical loading to become activated. To address this challenge, we synthesized magnetoplasmonic nanoparticles that can image, localize, and mechanically load targeted proteins with high spatiotemporal resolution. We demonstrate their utility by investigating the cell-surface activation of two mechanoreceptors: Notch and E-cadherin. By measuring cellular responses to a spectrum of spatial, chemical, temporal, and mechanical inputs at the single-molecule and single-cell levels, we reveal how spatial segregation and mechanical force cooperate to direct receptor activation dynamics. This generalizable technique can be used to control and understand diverse mechanosensitive processes in cell signaling. VIDEO ABSTRACT.
Assuntos
Técnicas Genéticas , Mecanotransdução Celular , Nanopartículas Metálicas , Receptores Notch/metabolismo , Actinas/metabolismo , Caderinas/metabolismo , Linhagem Celular , Células Cultivadas , Humanos , Mecanorreceptores/fisiologia , Nanopartículas Metálicas/química , Microesferas , Técnicas de Sonda Molecular , Proteínas Recombinantes de Fusão/metabolismo , Análise Espacial , TempoRESUMO
Quantitative detection of various molecules at very low concentrations in complex mixtures has been the main objective in many fields of science and engineering, from the detection of cancer-causing mutagens and early disease markers to environmental pollutants and bioterror agents1-5. Moreover, technologies that can detect these analytes without external labels or modifications are extremely valuable and often preferred6. In this regard, surface-enhanced Raman spectroscopy can detect molecular species in complex mixtures on the basis only of their intrinsic and unique vibrational signatures7. However, the development of surface-enhanced Raman spectroscopy for this purpose has been challenging so far because of uncontrollable signal heterogeneity and poor reproducibility at low analyte concentrations8. Here, as a proof of concept, we show that, using digital (nano)colloid-enhanced Raman spectroscopy, reproducible quantification of a broad range of target molecules at very low concentrations can be routinely achieved with single-molecule counting, limited only by the Poisson noise of the measurement process. As metallic colloidal nanoparticles that enhance these vibrational signatures, including hydroxylamine-reduced-silver colloids, can be fabricated at large scale under routine conditions, we anticipate that digital (nano)colloid-enhanced Raman spectroscopy will become the technology of choice for the reliable and ultrasensitive detection of various analytes, including those of great importance for human health.
Assuntos
Coloides , Imagem Individual de Molécula , Análise Espectral Raman , Coloides/química , Hidroxilamina/química , Nanopartículas Metálicas/química , Distribuição de Poisson , Estudo de Prova de Conceito , Reprodutibilidade dos Testes , Prata/química , Imagem Individual de Molécula/métodos , Imagem Individual de Molécula/normas , Análise Espectral Raman/métodos , Análise Espectral Raman/normas , VibraçãoRESUMO
The success of colloidal semiconductor nanocrystals (NCs) in science and optoelectronics is inextricable from their surfaces. The functionalization of lead halide perovskite NCs1-5 poses a formidable challenge because of their structural lability, unlike the well-established covalent ligand capping of conventional semiconductor NCs6,7. We posited that the vast and facile molecular engineering of phospholipids as zwitterionic surfactants can deliver highly customized surface chemistries for metal halide NCs. Molecular dynamics simulations implied that ligand-NC surface affinity is primarily governed by the structure of the zwitterionic head group, particularly by the geometric fitness of the anionic and cationic moieties into the surface lattice sites, as corroborated by the nuclear magnetic resonance and Fourier-transform infrared spectroscopy data. Lattice-matched primary-ammonium phospholipids enhance the structural and colloidal integrity of hybrid organic-inorganic lead halide perovskites (FAPbBr3 and MAPbBr3 (FA, formamidinium; MA, methylammonium)) and lead-free metal halide NCs. The molecular structure of the organic ligand tail governs the long-term colloidal stability and compatibility with solvents of diverse polarity, from hydrocarbons to acetone and alcohols. These NCs exhibit photoluminescence quantum yield of more than 96% in solution and solids and minimal photoluminescence intermittency at the single particle level with an average ON fraction as high as 94%, as well as bright and high-purity (about 95%) single-photon emission.
Assuntos
Desenho de Fármacos , Ligantes , Nanopartículas Metálicas , Pontos Quânticos , Acetona/química , Álcoois/química , Ânions , Compostos de Cálcio/química , Cátions , Coloides/química , Chumbo , Medições Luminescentes , Espectroscopia de Ressonância Magnética , Nanopartículas Metálicas/química , Simulação de Dinâmica Molecular , Óxidos/química , Fosfolipídeos/química , Pontos Quânticos/química , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Titânio/químicaRESUMO
Modern retrosynthetic analysis in organic chemistry is based on the principle of polar relationships between functional groups to guide the design of synthetic routes1. This method, termed polar retrosynthetic analysis, assigns partial positive (electrophilic) or negative (nucleophilic) charges to constituent functional groups in complex molecules followed by disconnecting bonds between opposing charges2-4. Although this approach forms the basis of undergraduate curriculum in organic chemistry5 and strategic applications of most synthetic methods6, the implementation often requires a long list of ancillary considerations to mitigate chemoselectivity and oxidation state issues involving protecting groups and precise reaction choreography3,4,7. Here we report a radical-based Ni/Ag-electrocatalytic cross-coupling of substituted carboxylic acids, thereby enabling an intuitive and modular approach to accessing complex molecular architectures. This new method relies on a key silver additive that forms an active Ag nanoparticle-coated electrode surface8,9 in situ along with carefully chosen ligands that modulate the reactivity of Ni. Through judicious choice of conditions and ligands, the cross-couplings can be rendered highly diastereoselective. To demonstrate the simplifying power of these reactions, concise syntheses of 14 natural products and two medicinally relevant molecules were completed.
Assuntos
Produtos Biológicos , Técnicas de Química Sintética , Descarboxilação , Eletroquímica , Eletrodos , Preparações Farmacêuticas , Ácidos Carboxílicos/química , Nanopartículas Metálicas/química , Oxirredução , Prata/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Níquel/química , Ligantes , Preparações Farmacêuticas/síntese química , Preparações Farmacêuticas/química , Eletroquímica/métodos , Técnicas de Química Sintética/métodosRESUMO
To construct tissue-like prosthetic materials, soft electroactive hydrogels are the best candidate owing to their physiological mechanical modulus, low electrical resistance and bidirectional stimulating and recording capability of electrophysiological signals from biological tissues1,2. Nevertheless, until now, bioelectronic devices for such prostheses have been patch type, which cannot be applied onto rough, narrow or deep tissue surfaces3-5. Here we present an injectable tissue prosthesis with instantaneous bidirectional electrical conduction in the neuromuscular system. The soft and injectable prosthesis is composed of a biocompatible hydrogel with unique phenylborate-mediated multiple crosslinking, such as irreversible yet freely rearrangeable biphenyl bonds and reversible coordinate bonds with conductive gold nanoparticles formed in situ by cross-coupling. Closed-loop robot-assisted rehabilitation by injecting this prosthetic material is successfully demonstrated in the early stage of severe muscle injury in rats, and accelerated tissue repair is achieved in the later stage.
Assuntos
Materiais Biocompatíveis , Hidrogéis , Próteses e Implantes , Ferimentos e Lesões , Animais , Ratos , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Condutividade Elétrica , Ouro/química , Hidrogéis/administração & dosagem , Hidrogéis/química , Hidrogéis/uso terapêutico , Nanopartículas Metálicas/química , Músculos/lesões , Músculos/inervação , Robótica , Ferimentos e Lesões/reabilitação , Ferimentos e Lesões/cirurgiaRESUMO
Chirality is a unifying structural metric of biological and abiological forms of matter. Over the past decade, considerable clarity has been achieved in understanding the chemistry and physics of chiral inorganic nanoparticles1-4; however, little is known about their effects on complex biochemical networks5,6. Intermolecular interactions of biological molecules and inorganic nanoparticles show some commonalities7-9, but these structures differ in scale, in geometry and in the dynamics of chiral shapes, which can both impede and strengthen their mirror-asymmetric complexes. Here we show that achiral and left- and right-handed gold biomimetic nanoparticles show different in vitro and in vivo immune responses. We use irradiation with circularly polarized light (CPL) to synthesize nanoparticles with controllable nanometre-scale chirality and optical anisotropy factors (g-factors) of up to 0.4. We find that binding of nanoparticles to two proteins from the family of adhesion G-protein-coupled receptors (AGPCRs)-namely cluster-of-differentiation 97 (CD97) and epidermal-growth-factor-like-module receptor 1 (EMR1)-results in the opening of mechanosensitive potassium-efflux channels, the production of immune signalling complexes known as inflammasomes, and the maturation of mouse bone-marrow-derived dendritic cells. Both in vivo and in vitro immune responses depend monotonically on the g-factors of the nanoparticles, indicating that nanoscale chirality can be used to regulate the maturation of immune cells. Finally, left-handed nanoparticles show substantially higher (1,258-fold) efficiency compared with their right-handed counterparts as adjuvants for vaccination against the H9N2 influenza virus, opening a path to the use of nanoscale chirality in immunology.
Assuntos
Proteínas de Ligação ao Cálcio , Células Dendríticas , Inflamassomos , Nanopartículas Metálicas , Receptores Acoplados a Proteínas G , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Células Dendríticas/imunologia , Ouro , Vírus da Influenza A Subtipo H9N2 , Mecanotransdução Celular , Nanopartículas Metálicas/química , Camundongos , Canais de Potássio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , EstereoisomerismoRESUMO
DNA has long been used as a template for the construction of helical assemblies of inorganic nanoparticles1-5. For example, gold nanoparticles decorated with DNA (or with peptides) can create helical assemblies6-9. But without such biological ligands, helices are difficult to achieve and their mechanism of formation is challenging to understand10,11. Atomically precise nanoclusters that are protected by ligands such as thiolate12,13 have demonstrated hierarchical structural complexity in their assembly at the interparticle and intraparticle levels, similar to biomolecules and their assemblies14. Furthermore, carrier dynamics can be controlled by engineering the structure of the nanoclusters15. But these nanoclusters usually have isotropic structures16,17 and often assemble into commonly found supercrystals18. Here we report the synthesis of homodimeric and heterodimeric gold nanoclusters and their self-assembly into superstructures. While the homodimeric nanoclusters form layer-by-layer superstructures, the heterodimeric nanoclusters self-assemble into double- and quadruple-helical superstructures. These complex arrangements are the result of two different motif pairs, one pair per monomer, where each motif bonds with its paired motif on a neighbouring heterodimer. This motif pairing is reminiscent of the paired interactions of nucleobases in DNA helices. Meanwhile, the surrounding ligands on the clusters show doubly or triply paired steric interactions. The helical assembly is driven by van der Waals interactions through particle rotation and conformational matching. Furthermore, the heterodimeric clusters have a carrier lifetime that is roughly 65 times longer than that of the homodimeric clusters. Our findings suggest new approaches for increasing complexity in the structural design and engineering of precision in supercrystals.
Assuntos
Ouro/química , Nanopartículas Metálicas/química , Cristalização , DNA/química , Ligantes , Modelos MolecularesRESUMO
The renal elimination pathway is increasingly harnessed to reduce nonspecific accumulation of engineered nanoparticles within the body and expedite their clinical applications. While the size of nanoparticles is recognized as crucial for their passive filtration through the glomerulus due to its limited pore size, the influence of nanoparticle charge on their transport and interactions within the kidneys remains largely elusive. Herein, we report that the proximal tubule and peritubular capillary, rather than the glomerulus, serve as primary charge barriers to the transport of charged nanoparticles within the kidney. Employing a series of ultrasmall, renal-clearable gold nanoparticles (AuNPs) with precisely engineered surface charge characteristics as multimodal imaging agents, we have tracked their distribution and retention across various kidney components following intravenous administration. Our results reveal that retention in the proximal tubules is governed not by the nanoparticle's zeta-potential, but by direct Coulombic interactions between the positively charged surface ligands of the AuNPs and the negatively charged microvilli of proximal tubules. However, further enhancing these interactions leads to increased binding of the positively charged AuNPs to the peritubular capillaries during the initial phase of elimination, subsequently facilitating their slow passage through the glomeruli and interaction with tubular components in a charge-selective manner. By identifying these two critical charge-dependent barriers in the renal transport of nanoparticles, our findings offer a fundamental insight for the design of renal nanomedicines tailored for selective targeting within the kidney, laying down a foundation for developing targeting renal nanomedicines for future kidney disease management in the clinics.
Assuntos
Ouro , Nanopartículas Metálicas , Ouro/química , Nanopartículas Metálicas/química , Animais , Camundongos , Túbulos Renais Proximais/metabolismo , Eliminação Renal , Rim/metabolismo , MasculinoRESUMO
In nature, DNA molecules carry the hereditary information. But DNA has physical and chemical properties that make it attractive for uses beyond heredity. In this Review, we discuss the potential of DNA for creating machines that are both encoded by and built from DNA molecules. We review the main methods of DNA nanostructure assembly, describe recent advances in building increasingly complex molecular structures and discuss strategies for creating machine-like nanostructures that can be actuated and move. We highlight opportunities for applications of custom DNA nanostructures as scientific tools to address challenges across biology, chemistry and engineering.
Assuntos
Membrana Celular/química , DNA/química , Sistemas de Liberação de Medicamentos , Nanopartículas Metálicas/química , Nanomedicina , Nanoestruturas/química , Animais , Biomimética , HumanosRESUMO
The quantum spin properties of nitrogen-vacancy defects in diamond enable diverse applications in quantum computing and communications1. However, fluorescent nanodiamonds also have attractive properties for in vitro biosensing, including brightness2, low cost3 and selective manipulation of their emission4. Nanoparticle-based biosensors are essential for the early detection of disease, but they often lack the required sensitivity. Here we investigate fluorescent nanodiamonds as an ultrasensitive label for in vitro diagnostics, using a microwave field to modulate emission intensity5 and frequency-domain analysis6 to separate the signal from background autofluorescence7, which typically limits sensitivity. Focusing on the widely used, low-cost lateral flow format as an exemplar, we achieve a detection limit of 8.2 × 10-19 molar for a biotin-avidin model, 105 times more sensitive than that obtained using gold nanoparticles. Single-copy detection of HIV-1 RNA can be achieved with the addition of a 10-minute isothermal amplification step, and is further demonstrated using a clinical plasma sample with an extraction step. This ultrasensitive quantum diagnostics platform is applicable to numerous diagnostic test formats and diseases, and has the potential to transform early diagnosis of disease for the benefit of patients and populations.
Assuntos
Técnicas Biossensoriais/métodos , Diagnóstico Precoce , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , HIV-1/genética , Nanodiamantes/química , RNA Viral/sangue , Avidina/química , Técnicas Biossensoriais/instrumentação , Biotina/química , Fluorescência , Ouro/química , HIV-1/isolamento & purificação , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Microfluídica/instrumentação , Microfluídica/métodos , Micro-Ondas , Técnicas de Amplificação de Ácido Nucleico , Papel , Plasma/virologia , Teoria Quântica , Sensibilidade e Especificidade , Imagem Individual de Molécula , TemperaturaRESUMO
Harnessing the programmable nature of DNA origami for controlling structural features in crystalline materials affords opportunities to bring crystal engineering to a remarkable level. However, the challenge of crystallizing a single type of DNA origami unit into varied structural outcomes remains, given the requirement for specific DNA designs for each targeted structure. Here, we show that crystals with distinct equilibrium phases and shapes can be realized using a single DNA origami morphology with an allosteric factor to modulate the binding coordination. As a result, origami crystals undergo phase transitions from a simple cubic lattice to a simple hexagonal (SH) lattice and eventually to a face-centered cubic (FCC) lattice. After selectively removing internal nanoparticles from DNA origami building blocks, the body-centered tetragonal and chalcopyrite lattice are derived from the SH and FCC lattices, respectively, revealing another phase transition involving crystal system conversions. The rich phase space was realized through the de novo synthesis of crystals under varying solution environments, followed by the individual characterizations of the resulting products. Such phase transitions can lead to associated transitions in the shape of the resulting products. Hexagonal prism crystals, crystals characterized by triangular facets, and twinned crystals are observed to form from SH and FCC systems, which have not previously been experimentally realized by DNA origami crystallization. These findings open a promising pathway toward accessing a rich phase space with a single type of building block and wielding other instructions as tools to develop crystalline materials with tunable properties.
Assuntos
Nanopartículas Metálicas , Nanoestruturas , Nanopartículas Metálicas/química , Magnésio , DNA/química , Cristalização , Transição de Fase , Nanotecnologia , Conformação de Ácido Nucleico , Nanoestruturas/químicaRESUMO
Selective and remote manipulation of activity for biomolecules, including protein, DNA, and lipids, is crucial to elucidate their molecular function and to develop biomedical applications. While advances in tool development, such as optogenetics, have significantly impacted these directions, the requirement for genetic modification significantly limits their therapeutic applications. Plasmonic nanoparticle heating has brought new opportunities to the field, as hot nanoparticles are unique point heat sources at the nanoscale. In this review, we summarize fundamental engineering problems such as plasmonic heating and the resulting biomolecular responses. We highlight the biological responses and applications of manipulating biomolecules and provide perspectives for future directions in the field.
Assuntos
DNA , DNA/química , Humanos , Proteínas/química , Optogenética/métodos , Animais , Nanopartículas/química , Nanotecnologia/métodos , Lipídeos/química , Nanopartículas Metálicas/química , Ressonância de Plasmônio de Superfície , Temperatura AltaRESUMO
ConspectusDNA-stabilized silver nanoclusters (AgN-DNAs) are sequence-encoded fluorophores. Like other noble metal nanoclusters, the optical properties of AgN-DNAs are dictated by their atomically precise sizes and shapes. What makes AgN-DNAs unique is that nanocluster size and shape are controlled by nucleobase sequence of the templating DNA oligomer. By choice of DNA sequence, it is possible to synthesize a wide range of AgN-DNAs with diverse emission colors and other intriguing photophysical properties. AgN-DNAs hold significant potential as "programmable" emitters for biological imaging due to their combination of small molecular-like sizes, bright and sequence-tuned fluorescence, low toxicities, and cost-effective synthesis. In particular, the potential to extend AgN-DNAs into the second near-infrared region (NIR-II) is promising for deep tissue imaging, which is a major area of interest for advancing biomedical imaging. Achieving this goal requires a deep understanding of the structure-property relationships that govern AgN-DNAs in order to design AgN-DNA emitters with sizes and geometries that support NIR-II emission.In recent years, major advances have been made in understanding the structure and composition of AgN-DNAs, enabling new insights into the correlation of nanocluster structure and photophysical properties. These advances have hinged on combined innovations in mass characterization and crystallography of compositionally pure AgN-DNAs, together with combinatorial experiments and machine learning-guided design. A combined approach is essential due to the major challenge of growing suitable AgN-DNA crystals for diffraction and to the labor-intensive nature of preparing and solving the molecular formulas of atomically precise AgN-DNAs by mass spectrometry. These approaches alone are not feasibly scaled to explore the large sequence space of DNA oligomer templates for AgN-DNAs.This account describes recent fundamental advances in AgN-DNA science that have been enabled by high throughput synthesis and fluorimetry together with detailed analytical studies of purified AgN-DNAs. First, short introductions to nanocluster chemistry and AgN-DNA basics are presented. Then, we review recent large-scale studies that have screened thousands of DNA templates for AgN-DNAs, leading to discovery of distinct classes of these emitters with unique cluster core compositions and ligand chemistries. In particular, the discovery of a new class of chloride-stabilized AgN-DNAs enabled the first ab initio calculations of AgN-DNA electronic structure and present new approaches to stabilize these emitters in biologically relevant conditions. Near-infrared (NIR) emissive AgN-DNAs are also found to exhibit diverse structures and properties. Finally, we conclude by highlighting recent proof-of-principle demonstrations of NIR AgN-DNAs for targeted fluorescence imaging. Continued efforts may future push AgN-DNAs into the tissue transparency window for fluorescence imaging in the NIR-II tissue transparency window.
Assuntos
DNA , Nanopartículas Metálicas , Prata , Prata/química , DNA/química , Nanopartículas Metálicas/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese químicaRESUMO
Lung cancer is the leading cause of mortality worldwide of which non-small cell lung carcinoma constitutes majority of the cases. High mortality is attributed to early metastasis, late diagnosis, ineffective treatment and tumor relapse. Chemotherapy and radiotherapy form the mainstay of its treatment. However, their associated side effects involving kidneys, nervous system, gastrointestinal tract, and liver further adds to dismal outcome. These disadvantages of conventional treatment can be circumvented by use of engineered nanoparticles for improved effectiveness with minimal side effects. In this study we have synthesized silver gold nanocomposite (Ag-Au NC) using polyethylene glycol and l-ascorbic acid as surfactant and reducing agent respectively. Synthesized nanocomposite was characterized by ultraviolet-visible absorption, dynamic light scattering, scanning and transmission electron microscopy. Compositional analysis was carried out by energy dispersive X-ray analysis and average pore diameter was estimated using Barrett-Joyner-Halenda method. In-silico molecular docking analysis of the synthesized NC against active regions of epidermal growth factor receptor revealed good binding energy. Subsequently, we investigated the effect of NC on growth and stem cell attributes of A549 lung cancer cells. Results showed that NC was effective in inhibiting A549 cell proliferation, induced DNA damage, G2/M phase arrest and apoptosis. Further, tumor cell migration and spheroid formation were also negatively affected. NC also enhanced reactive oxygen species generation and mitochondrial depolarization. In addition, the effect of NC on putative cancer stem cells in A549 cells was evaluated. We found that Ag-Au NC at IC50 targeted CD44, CD24, CD166, CD133 and CD326 positive cancer stem cells and induced apoptosis. CD166 positive cells were relatively resistance to apoptosis. Together our results demonstrate the anticancer efficacy of Ag-Au NC mediated by a mechanism involving cell cycle arrest and mitochondrial derangement.
Assuntos
Neoplasias Pulmonares , Nanopartículas Metálicas , Nanocompostos , Humanos , Neoplasias Pulmonares/patologia , Ácido Ascórbico/farmacologia , Simulação de Acoplamento Molecular , Apoptose , Pulmão/metabolismo , Nanocompostos/química , Células-Tronco Neoplásicas/metabolismo , Nanopartículas Metálicas/química , Linhagem Celular TumoralRESUMO
Effective antitumor immunity in mice requires activation of the type I interferon (IFN) response pathway. IFNα and IFNß therapies have proven promising in humans, but suffer from limited efficacy and high toxicity. Intratumoral IFN retention ameliorates systemic toxicity, but given the complexity of IFN signaling, it was unclear whether long-term intratumoral retention of type I IFNs would promote or inhibit antitumor responses. To this end, we compared the efficacy of IFNα and IFNß that exhibit either brief or sustained retention after intratumoral injection in syngeneic mouse tumor models. Significant enhancement in tumor retention, mediated by anchoring these IFNs to coinjected aluminum-hydroxide (alum) particles, greatly improved both their tolerability and efficacy. The improved efficacy of alum-anchored IFNs could be attributed to sustained pleiotropic effects on tumor cells, immune cells, and nonhematopoietic cells. Alum-anchored IFNs achieved high cure rates of B16F10 tumors upon combination with either anti-PD-1 antibody or interleukin-2. Interestingly however, these alternative combination immunotherapies yielded disparate T cell phenotypes and differential resistance to tumor rechallenge, highlighting important distinctions in adaptive memory formation for combinations of type I IFNs with other immunotherapies.
Assuntos
Hidróxido de Alumínio , Imunoterapia , Interferon Tipo I , Compostos de Alúmen/química , Hidróxido de Alumínio/química , Animais , Antineoplásicos/uso terapêutico , Modelos Animais de Doenças , Humanos , Imunoterapia/métodos , Imunoterapia/normas , Interferon Tipo I/química , Interferon Tipo I/uso terapêutico , Interferon-alfa , Interferon beta , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , CamundongosRESUMO
Advancements in nanochemistry have led to the development of engineered gold nanostructures (GNSs) with remarkable potential for a variety of dental healthcare applications. These innovative nanomaterials offer unique properties and functionalities that can significantly improve dental diagnostics, treatment, and overall oral healthcare applications. This review provides an overview of the latest advancements in the design, synthesis, and application of GNSs for dental healthcare applications. Engineered GNSs have emerged as versatile tools, demonstrating immense potential across different aspects of dentistry, including enhanced imaging and diagnosis, prevention, bioactive coatings, and targeted treatment of oral diseases. Key highlights encompass the precise control over GNSs' size, crystal structure, shape, and surface functionalization, enabling their integration into sensing, imaging diagnostics, drug delivery systems, and regenerative therapies. GNSs, with their exceptional biocompatibility and antimicrobial properties, have demonstrated efficacy in combating dental caries, periodontitis, peri-implantitis, and oral mucosal diseases. Additionally, they show great promise in the development of advanced sensing techniques for early diagnosis, such as nanobiosensor technology, while their role in targeted drug delivery, photothermal therapy, and immunomodulatory approaches has opened new avenues for oral cancer therapy. Challenges including long-term toxicity, biosafety, immune recognition, and personalized treatment are under rigorous investigation. As research at the intersection of nanotechnology and dentistry continues to thrive, this review highlights the transformative potential of engineered GNSs in revolutionizing dental healthcare, offering accurate, personalized, and minimally invasive solutions to address the oral health challenges of the modern era.
Assuntos
Ouro , Ouro/química , Humanos , Propriedades de Superfície , Nanopartículas Metálicas/química , Odontologia , Sistemas de Liberação de Medicamentos , Nanotecnologia/métodosRESUMO
Proteins are an eminently important class of ubiquitous biomacromolecules with diverse biological functions, and numerous techniques for their detection, quantification, and localisation have been developed. Many of these methods exploit the selectivity arising from molecular recognition of proteins/antigens by immunoglobulins. The combination of surface-enhanced Raman scattering (SERS) with such "immuno"-techniques to immuno-SERS (iSERS) is the central topic of this review, which is focused on colloidal SERS nanotags, i.e., molecularly functionalised noble metal nanoparticles conjugated to antibodies, for their use in protein assays and ex vivo imaging. After contrasting the fundamental differences between label-free SERS and iSERS, including a balanced description of the advantages and drawbacks of the latter, we describe the usual workflow of iSERS experiments. Milestones in the development of the iSERS technology are summarised from a historical perspective. By highlighting selected examples from the literature, we illustrate the conceptual progress that has been achieved in the fields of iSERS-based protein assays and ex vivo imaging. Finally, we attempt to predict what is necessary to fully exploit the transformative potential of the iSERS technology by stimulating the transition from research in academic labs into applications for the benefit of our society.
Assuntos
Proteínas , Análise Espectral Raman , Proteínas/química , Proteínas/análise , Humanos , Nanopartículas Metálicas/química , AnimaisRESUMO
Silver and gold nanoparticles have found extensive biomedical applications due to their strong localized surface plasmon resonance (LSPR) and intriguing plasmonic properties. This review article focuses on the correlation among particle geometry, plasmon properties and biomedical applications. It discusses how particle shape and size are tailored via controllable synthetic approaches, and how plasmonic properties are tuned by particle shape and size, which are embodied by nanospheres, nanorods, nanocubes, nanocages, nanostars and core-shell composites. This article summarizes the design strategies for the use of silver and gold nanoparticles in plasmon-enhanced fluorescence, surface-enhanced Raman scattering (SERS), electroluminescence, and photoelectrochemistry. It especially discusses how to use plasmonic nanoparticles to construct optical probes including colorimetric, SERS and plasmonic fluorescence probes (labels/reporters). It also demonstrates the employment of Ag and Au nanoparticles in polymer- and paper-based microfluidic devices for point-of-care testing (POCT). In addition, this article highlights how to utilize plasmonic nanoparticles for in vitro and in vivo bio-imaging based on SERS, fluorescence, photoacoustic and dark-field models. Finally, this article shows perspectives in plasmon-enhanced photothermal and photodynamic therapy.
Assuntos
Ouro , Nanopartículas Metálicas , Ouro/química , Prata/química , Nanopartículas Metálicas/química , Ressonância de Plasmônio de Superfície/métodos , Análise Espectral Raman/métodosRESUMO
Advances in surface-enhanced Raman scattering (SERS) detection have helped to overcome the limitations of traditional in vitro diagnostic methods, such as fluorescence and chemiluminescence, owing to its high sensitivity and multiplex detection capability. However, for the implementation of SERS detection technology in disease diagnosis, a SERS-based assay platform capable of analyzing clinical samples is essential. Moreover, infectious diseases like COVID-19 require the development of point-of-care (POC) diagnostic technologies that can rapidly and accurately determine infection status. As an effective assay platform, SERS-based bioassays utilize SERS nanotags labeled with protein or DNA receptors on Au or Ag nanoparticles, serving as highly sensitive optical probes. Additionally, a microdevice is necessary as an interface between the target biomolecules and SERS nanotags. This review aims to introduce various microdevices developed for SERS detection, available for POC diagnostics, including LFA strips, microfluidic chips, and microarray chips. Furthermore, the article presents research findings reported in the last 20 years for the SERS-based bioassay of various diseases, such as cancer, cardiovascular diseases, and infectious diseases. Finally, the prospects of SERS bioassays are discussed concerning the integration of SERS-based microdevices and portable Raman readers into POC systems, along with the utilization of artificial intelligence technology.
Assuntos
Técnicas Biossensoriais , COVID-19 , Análise Espectral Raman , Humanos , COVID-19/diagnóstico , COVID-19/virologia , Nanopartículas Metálicas/química , SARS-CoV-2/isolamento & purificação , Sistemas Automatizados de Assistência Junto ao Leito , Ouro/químicaRESUMO
To date, studies on the thermodynamic and kinetic processes that underlie biological function and nanomachine actuation in biological- and biology-inspired molecular constructs have primarily focused on photothermal heating of ensemble systems, highlighting the need for probes that are localized within the molecular construct and capable of resolving single-molecule response. Here we present an experimental demonstration of wavelength-selective, localized heating at the single-molecule level using the surface plasmon resonance of a 15 nm gold nanoparticle (AuNP). Our approach is compatible with force-spectroscopy measurements and can be applied to studies of the single-molecule thermodynamic properties of DNA origami nanomachines as well as biomolecular complexes. We further demonstrate wavelength selectivity and establish the temperature dependence of the reaction coordinate for base-pair disruption in the shear-rupture geometry, demonstrating the utility and flexibility of this approach for both fundamental studies of local (nanometer-scale) temperature gradients and rapid and multiplexed nanomachine actuation.