RESUMEN
Although nanotechnology often addresses biomedical needs, nanoscale tools can also facilitate broad biological discovery. Nanoscale delivery, imaging, biosensing, and bioreactor technologies may address unmet questions at the interface between chemistry and biology. Currently, many chemical biologists do not include nanomaterials in their toolbox, and few investigators develop nanomaterials in the context of chemical tools to answer biological questions. We reason that the two fields are ripe with opportunity for greater synergy. Nanotechnologies can expand the utility of chemical tools in the hands of chemical biologists, for example, through controlled delivery of reactive and/or toxic compounds or signal-binding events of small molecules in living systems. Conversely, chemical biologists can work with nanotechnologists to address challenging biological questions that are inaccessible to both communities. This Perspective aims to introduce the chemical biology community to nanotechnologies that may expand their methodologies while inspiring nanotechnologists to address questions relevant to chemical biology.
Asunto(s)
Biología Molecular/tendencias , Nanotecnología/tendencias , Animales , Materiales Biocompatibles , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Enzimas/química , Humanos , Biología Molecular/métodos , Imagen Molecular/métodos , NanopartículasRESUMEN
Hematoxylin & eosin (H&E) is the gold standard histological stain used for medical diagnosis and has been used for over a century. Herein, we examined the near-infrared II (NIR-II) fluorescence of this stain. We observed significant NIR-II emission from the hematoxylin component of the H&E stain. We found that the emission intensity, using the common aluminum(III) hematoxylin mordant, could be modulated by the availability of endogenous iron(III), and this emission intensity increased at higher oxidative stress. Our mechanistic investigations found that hematoxylin emission reported the nuclear translocation of the iron via the protein ferritin. In human tumor tissue samples, oxidative stress biomarkers correlated with hematoxylin NIR-II emission intensity. Emission response of the stain was also observed in human Alzheimer's disease brain tissue regions affected by disease progression, suggesting that ferritin nuclear translocation is preserved in these regions as an oxidative stress response. These findings indicate that NIR-II emission from the H&E stain provides a new source of redox information in tissues with implications for biomedical research and clinical practice.
Asunto(s)
Colorantes , Estrés Oxidativo , Humanos , Eosina Amarillenta-(YS) , Compuestos Férricos , Ferritinas , Hematoxilina , Hierro , Estrés Oxidativo/fisiologíaRESUMEN
We describe three new strategies for determining heterogeneous reaction rates using photomicroscopy to measure the rate of retreat of metal surfaces: (i) spheres in a stirred solution, (ii) microscopic powder in an unstirred solution, and (iii) spheres on a rotating shaft. The strategies are applied to indium-mediated allylation (IMA), which is a powerful tool for synthetic chemists because of its stereoselectivity, broad applicability, and high yields. The rate-limiting step of IMA, reaction of allyl halides at indium metal surfaces, is shown to be fast, with a minimum value of the heterogeneous rate constant of 1 × 10(-2) cm/s, an order of magnitude faster than the previously determined minimum value. The strategies described here can be applied to any reaction in which the surface is retreating or advancing, thereby broadening the applicability of photomicroscopy to measuring heterogeneous reaction kinetics.
Asunto(s)
Compuestos Alílicos/síntesis química , Indio/química , Compuestos Organometálicos/química , Compuestos Alílicos/química , Hidrocarburos Halogenados/química , Estructura Molecular , Compuestos Organometálicos/síntesis química , Tamaño de la Partícula , Fotomicrografía , Soluciones , Estereoisomerismo , Propiedades de SuperficieRESUMEN
Single-walled carbon nanotubes are of interest in biomedicine for imaging and molecular sensing applications and as shuttles for various cargos such as chemotherapeutic drugs, peptides, proteins, and oligonucleotides. Carbon nanotube surface chemistry can be modulated for subcellular targeting while preserving photoluminescence for label-free visualization in complex biological environments, making them attractive materials for such studies. The cell nucleus is a potential target for many pathologies including cancer and infectious diseases. Understanding mechanisms of nanomaterial delivery to the nucleus may facilitate diagnostics, drug development, and gene-editing tools. Currently, there are no systematic studies to understand how these nanomaterials gain access to the nucleus. Herein, we developed a carbon nanotube based hybrid material that elucidate a distinct mechanism of nuclear translocation of a nanomaterial in cultured cells. We developed a nuclear-targeted probe via cloaking photoluminescent single-walled carbon nanotubes in a guanidinium-functionalized helical polycarbodiimide. We found that the nuclear entry of the nanotubes was mediated by the import receptor importin ß without the aid of importin α and not by the more common importin α/ß pathway. Additionally, the nanotube photoluminescence exhibited distinct red-shifting upon entry to the nucleus, potentially functioning as a reporter of the importin ß-mediated nuclear transport process. This work delineates a noncanonical mechanism for nanomaterial delivery to the nucleus and provides a reporter for the study of nucleus-related pathologies.
Asunto(s)
Núcleo Celular/metabolismo , Sustancias Luminiscentes/metabolismo , Nanotubos de Carbono/análisis , Imagen Óptica , Transporte Activo de Núcleo Celular , Células HeLa , Humanos , Sustancias Luminiscentes/química , Microscopía Fluorescente , Estructura Molecular , Nanotubos de Carbono/química , Polímeros/química , Células Tumorales CultivadasRESUMEN
Carbon nanotube-based molecular probes, imaging agents, and biosensors in cells and in vivo continue to garner interest as investigational tools and clinical devices due to their unique photophysical properties. Surface chemistry modulation of nanotubes plays a critical role in determining stability and interaction with biological systems both in vitro and in vivo. Among the many parameters that influence the biological fate of nanomaterials, surface charge is particularly influential due to direct electrostatic interactions with components of the cell membrane as well as proteins in the serum, which coat the nanoparticle surface in a protein corona and alter nanoparticle-cell interactions. Here, we modulated functional moieties on a helical polycarbodiimide polymer backbone that non-covalently suspended the nanotubes in aqueous media. By derivatizing the polymer with either primary amine or carboxylic acid side chains, we obtained nanotube complexes that present net surface charges of opposite polarity at physiological pH. Using these materials, we found that the uptake of carbon nanotubes in these cells is highly dependent on charge, with cationic nanotubes efficiently internalized into cells compared to the anionic nanotubes. Furthermore, we found that serum proteins drastically influenced cell uptake of the anionic nanotubes, while the effect was not prominent for the cationic nanotubes. Our findings have implications for improved engineering of drug delivery devices, molecular probes, and biosensors.