Добірка наукової літератури з теми "Multifunctional Inorganic Nanoparticles for Biomedical Diagnostics"

Hybrid nanoarchitectures such as magnetic polymeric micelles (MPMs) are among the most promising nanotechnology-enabled materials for biomedical applications combining the benefits of polymeric micelles and magnetic nanoparticles within a single bioinstructive system. MPMs are formed by the self-assembly of polymer amphiphiles above the critical micelle concentration, generating a colloidal structure with a hydrophobic core and a hydrophilic shell incorporating magnetic particles (MNPs) in one of the segments. MPMs have been investigated most prominently as contrast agents for magnetic resonance imaging (MRI), as heat generators in hyperthermia treatments, and as magnetic-susceptible nanocarriers for the delivery and release of therapeutic agents. The versatility of MPMs constitutes a powerful route to ultrasensitive, precise, and multifunctional diagnostic and therapeutic vehicles for the treatment of a wide range of pathologies. Although MPMs have been significantly explored for MRI and cancer therapy, MPMs are multipurpose functional units, widening their applicability into less expected fields of research such as bioengineering and regenerative medicine. Herein, we aim to review published reports of the last five years about MPMs concerning their structure and fabrication methods as well as their current and foreseen expectations for advanced biomedical applications.

Iron oxide nanoparticles are a promising platform for biomedical applications, both in terms of diagnostics and therapeutics. In addition, arginine-rich polypeptides are known to penetrate across cell membranes. Here, we thus introduce a system based on magnetite nanoparticles and the polypeptide poly-l-arginine (polyR-Fe3O4). We show that the hybrid nanoparticles exhibit a low cytotoxicity that is comparable to Resovist®, a commercially available drug. PolyR-Fe3O4 particles perform very well in diagnostic applications, such as magnetic particle imaging (1.7 and 1.35 higher signal respectively for the 3rd and 11th harmonic when compared to Resovist®), or as contrast agents for magnetic resonance imaging (R2/R1 ratio of 17 as compared to 11 at 0.94 T for Resovist®). Moreover, these novel particles can also be used for therapeutic purposes such as hyperthermia, achieving a specific heating power ratio of 208 W/g as compared to 83 W/g for Feridex®, another commercially available product. Therefore, we envision such materials to play a role in the future theranostic applications, where the arginine ability to deliver cargo into the cell can be coupled to the magnetite imaging properties and cancer fighting activity.

Due to their good magnetic properties, excellent biocompatibility, and low price, magnetic iron oxide nanoparticles (IONPs) are the most commonly used magnetic nanomaterials and have been extensively explored in biomedical applications. Although magnetic IONPs can be used for a variety of applications in biomedicine, most practical applications require IONP-based platforms that can perform several tasks in parallel. Thus, appropriate engineering and integration of magnetic IONPs with different classes of organic and inorganic materials can produce multifunctional nanoplatforms that can perform several functions simultaneously, allowing their application in a broad spectrum of biomedical fields. This review article summarizes the fabrication of current composite nanoplatforms based on integration of magnetic IONPs with organic dyes, biomolecules (e.g., lipids, DNAs, aptamers, and antibodies), quantum dots, noble metal NPs, and stimuli-responsive polymers. We also highlight the recent technological advances achieved from such integrated multifunctional platforms and their potential use in biomedical applications, including dual-mode imaging for biomolecule detection, targeted drug delivery, photodynamic therapy, chemotherapy, and magnetic hyperthermia therapy.

Molecularly imprinted polymers (MIPs) continue to gain increasing attention as functional materials due to their unique characteristics such as higher stability, simple preparation, robustness, better binding capacity, and low cost. In particular, MIP-coated inorganic nanoparticles have emerged as a promising platform for various biomedical applications ranging from drug delivery to bioimaging. The integration of MIPs with inorganic nanomaterials such as silica (SiO2), iron oxide (Fe3O4), gold (Au), silver (Ag), and quantum dots (QDs) combines several attributes from both components to yield highly multifunctional materials. These materials with a multicomponent hierarchical structure composed of an inorganic core and an imprinted polymer shell exhibit enhanced properties and new functionalities. This review aims to provide a general overview of key recent advances in the fabrication of MIPs-coated inorganic nanoparticles and highlight their biomedical applications, including drug delivery, biosensor, bioimaging, and bioseparation.

This review gives a broad introduction to nanotechnology, mesoporous silica nanoparticles (MSNs) and synthesis techniques, along with their applications. Recent advances in morphological control and surface functionalization of MSNs have improved their biocompatibility and a strong emphasis on the physicochemical characteristics of MSNs, resulting in a step forward in traditional intervention techniques. This review highlights recent improvements in silica-assisted drug delivery systems including MSN-based sustained drug delivery systems and MSN-based controlled, targeted drug delivery systems. Silica nanoparticles can be used to blend different materials, mix different functions and be a cornerstone for a multifunctional nanomedicine podium for multimodal imaging and diagnostics therapy.

Background: Biomedical applications of Magnetic Nanoparticles (MNPs) are creating a major impact on disease diagnosis and nanomedicine or a combined platform called theranostics. A significant progress has been made to engineer novel and hybrid MNPs for their multifunctional modalities such as imaging, biosensors, chemotherapeutic or photothermal and antimicrobial agents. MNPs are successfully applied in biomedical applications due to their unique and tunable properties such as superparamagnetism, stability, and biocompatibility. Approval of ferumoxytol (feraheme) for MRI and the fact that several Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are currently undergoing clinical trials have paved a path for future MNPs formulations. Intensive research is being carried out in designing and developing novel nanohybrids for multiple applications in nanomedicine. Objective: The objective of the present review is to summarize recent developments of MNPs in imaging modalities like MRI, CT, PET and PA, biosensors and nanomedicine including their role in targeting and drug delivery. Relevant theory and examples of the use of MNPs in these applications have been cited and discussed to create a thorough understanding of the developments in this field. Conclusion: MNPs have found widespread use as contrast agents in imaging modalities, as tools for bio-sensing, and as therapeutic and theranostics agents. Multiple formulations of MNPs are in clinical testing and may be accepted in clinical settings in near future.

AbstractNanoparticles for biomedical applications have several advantages as multifunctional agents. Among various types of nanoparticles for biomedical applications, silica nanoparticles have characteristic positioning due to their inherent property. The recent development of silica nanoparticles is creating a new trend in nanomedicine. A novel type of silica nanoparticle, organosilica nanoparticle, is both structurally and functionally different from the common (inorgano)silica nanoparticle. The organosilica nanoparticles are inherent organic-inorganic hybrid nanomaterials. The interior and exterior functionalities of organosilica nanoparticles are useful for their multifunctionalization. Biomedical applications of organosilica nanoparticles are leading to a wide range of nanomedical fields such as basic biomedical investigations and clinical applications. Multifunctionalizations peculiar to organosilica nanoparticles enable the creation of novel imaging systems and therapeutic applications. In this review, I will introduce differences between (inorgano)silica nanoparticles and organosilica nanoparticles, and then focus on biomedical applications of organosilica nanoparticles toward theranostics.

The field of nanotechnology has emerged as a promising course of study branching out into various biomedical fields such as therapeutics, imaging, and diagnostics. Metallic nanoparticles, specifically silver, are an important area of study due to their multifunctionality and diverse morphological characteristics. Amongst the various methods of synthesis of these multifunctional nanoparticles such as physical methods and chemical, green synthesis is the most suitable method due to its eco-friendly nature, cost-effectiveness, and ease of production. This article summarizes the broad spectrum of applications of green silver nanoparticles in the fields of cancer theranostics, imaging and diagnosis, and drug delivery. Bimetallic nanoparticles with silver as one of its major constituents are also explored to get a clear insight into the numerous prospective developments in the respective field.

Electrospun hybrid nanofibers, based on functional agents immobilized in polymeric matrix, possess a unique combination of collective properties. These are beneficial for a wide range of applications, which include theranostics, filtration, catalysis, and tissue engineering, among others. The combination of functional agents in a nanofiber matrix offer accessibility to multifunctional nanocompartments with significantly improved mechanical, electrical, and chemical properties, along with better biocompatibility and biodegradability. This review summarizes recent work performed for the fabrication, characterization, and optimization of different hybrid nanofibers containing varieties of functional agents, such as laser ablated inorganic nanoparticles (NPs), which include, for instance, gold nanoparticles (Au NPs) and titanium nitride nanoparticles (TiNPs), perovskites, drugs, growth factors, and smart, inorganic polymers. Biocompatible and biodegradable polymers such as chitosan, cellulose, and polycaprolactone are very promising macromolecules as a nanofiber matrix for immobilizing such functional agents. The assimilation of such polymeric matrices with functional agents that possess wide varieties of characteristics require a modified approach towards electrospinning techniques such as coelectrospinning and template spinning. Additional focus within this review is devoted to the state of the art for the implementations of these approaches as viable options for the achievement of multifunctional hybrid nanofibers. Finally, recent advances and challenges, in particular, mass fabrication and prospects of hybrid nanofibers for tissue engineering and biomedical applications have been summarized.

La investigación presentada en esta tesis incluye la síntesis y caracterización de ácidos carboranilfosfínicos y carboranilfosfónicos para utilizarlos como bloques versátiles puramente inorgánicos. En el Capítulo 2 se ha demostrado que, de manera similar a los fosfinatos orgánicos, se pueden preparar carboranilfosfinatos puramente inorgánicos en rendimientos de muy buenos a excelentes, mientras que la preparación de carboranilfosfonatos no sigue la misma tendencia. Los carboranilfosfonatos no se pueden preparar tan fácilmente, al menos con los métodos descritos en la presente tesis doctoral (Capítulo 3). Los ácidos carboranilfosfínicos se han preparado tanto con el orto- como con el meta-carborano. El hidrógeno en la unidad H-P del carboranilfosfinato ha sido fácilmente intercambiado por D en el disolvente de RMN deuterado, aunque se han observado diferencias en las velocidades de dicho intercambio dependiendo del sustituyente adyacente al Cc de carborano y de la sal utilizada. La influencia del carborano se ha observado en el pK del fosfinato, que es más negativo para el m-carboranilo y más positivo para el o-carboranilo, comparados con el fenilo. Teniendo suficiente información sobre los diferentes ácidos fosfínicos del orto- y meta-carborano, para su uso posterior ponemos nuestra atención en los derivados del meta-carborano, debido a su estabilidad mejorada comparada con los derivados orto-isómeros. En el capítulo 4 hemos estudiado la química de coordinación de ligandos de m-carboranilfosfinato con el primer y el segundo período de metales de transición en medios de alcohol e iniciamos estudios en el medio acuoso, con el objetivo de generar polímeros de coordinación puramente inorgánicos (CPs). Las estructuras de rayos X muestran CPs 1D de fosfinato de MnII y CdII y la formación de sales de CoII y NiII. También, se ha sintetizado un nuevo polímero 1D con ZnII y un compuesto de CuII dinuclear unidos por puentes carboranilfosfinato. La estructura polimérica 1D del polímero de coordinación MnII se mantiene en presencia del ligando quelante 2,2'-bpy, generando un nuevo compuesto polimérico 1D de MnII. Por otro lado la reactividad de CPs de MnII con agua condujo a la rotura de los polímeros en fragmentos de baja nuclearidad. Contrariamente, la estructura polimérica CP de CdII permanece en presencia de H2O. Se realizaron medidas magnéticas de compuestos polinucleares de manganeso mostrando en todos los casos interacciones antiferromagnéticas débiles entre los átomos de manganeso. Además, en el Capítulo 4 se describen algunos estudios de la reactividad de 1-R-7-OPH(OH)-1,7-closo-C2B10H10 y Na[1-OPH(O)-1,7-closo-C2B10H11] (R = CH3, H) con MnII y CoII en medio acuoso, lo que revela que el sustituyente -CH3 o -H, en uno de los Cc del ligando de carboranilfosfinato y el sustrato metálico (MnCO3 o MnCl2) define la estructura final del complejo. Por lo tanto, se encontró que el sustituyente -CH3 en el Cc era favorable a la formación de complejos polinucleares, mientras que el sustituyente -H en el Cc es favorable para los complejos o sales mononucleares. La última parte de la tesis (Capítulo 5) se refiere a la capacidad del nuevo ligando de carboranilfosfinato para unirse a la superficie de nanopartículas magnéticas (MNPs) a través de la coordinación a los átomos de hierro como un ligando puente fosfinato bidentado (1-MNPs), y permite comprender cómo el ambiente influye en la fuerza de este vínculo. De particular relevancia en lo que se refiere a la estabilidad de 1-MNPs antes y después de la esterilización en condiciones de autoclave. Los estudios biológicos confirmaron la captación de 1-MNPs por las células cultivadas (hCMEC / D3 y A172) y la presencia del m-carboranilfosfinato en muestras de células secas. La cuantificación de la captación de 1-MNPs por células mostró que las células A172 de glioblastoma presentaban contenidos de hierro celular más grandes que las células endoteliales cerebrales (hCMEC / D3). En cuanto a la seguridad de los fármacos, hemos demostrado que la administración sistematica de los nanohíbridos de 1-MNPs no muestra signos de toxicidad en ratones, apoyando su posible traducción al entorno biomédico.
The research presented in this thesis includes the synthesis and characterization of carboranylphosphinic and carboranylphosphonic acids to use them as versatile purely inorganic building blocks. In the Chapter 2 has been shown that, in a similar manner to organic phosphinates, purely inorganic carboranyl-phosphinates can be prepared in very good to excellent yields, while the preparation of carboranylphosphonates does not follow the same tendency. Carboranylphosphonates cannot be so easily made, at least with described in this PhD thesis methods (Chapter 3). Carboranylphosphinic acids have been prepared both with the ortho-, and meta-carborane. The hydrogen in the H–P unit of the carboranylphosphinate has been easily exchanged by D from the deuterated NMR solvent, although rate differences have been noticed depending on the adjacent carborane carbon substituent and the salt utilized. The carborane influence has been noticed in the pK of the phosphinate, which is more negative for the m-carboranyl and more positive for the o-carboranyl when are compared with the organic phenyl. Having enough information on the different phosphinic acids of ortho- and meta-carborane, for further use we put our attention on the meta-carborane derivatives due to its enhanced stability compare to ortho-isomer derivatives. In the Chapter 4 we have studied the coordination chemistry of m-carboranylphosphinate ligands with the first and the second raw transition metals in alcohol media and initiated studies in aqueous media, aiming to generate purely inorganic coordination polymers (CPs). The X-Ray structures show 1D phosphinate CPs of MnII and CdII and the formation of salts of CoII and NiII. Also, a new 1D polymer with ZnII and a carboranylphosphinate bridged dinuclear CuII compound have been synthesized. The polymeric structure of MnII coordination polymer was maintained in the presence of 2,2’-bpy chelating ligand generating a new 1D polymeric manganese derivative, while the reactivity of MnII CPs with water led to the breakage of the polymers into fragments of low nuclearity. Contrary, the polymeric structure of CdII CP remains in the presence of H2O. Magnetic measurements of manganese polynuclear compounds were carried out showing in all cases, weak antiferromagnetic interactions between the manganese atoms. Further, in the Chapter 4 we describe some studies of the reactivity of 1-R-7-OPH(OH)-1,7-closo-C2B10H10 and Na[1-OPH(O)-1,7-closo-C2B10H11] (R= CH3, H) ligands with MnII and CoII in aqueous media revealing that the substituent, -CH3 or -H, on the other C of the cluster of the carboranylphosphinate ligand and the starting metal salt (MnCO3 or MnCl2) can play a role in the final molecular structure of the complex. Thus, the –CH3 substituent at the Cc was found to be favorable to produce polynuclear complexes, while the –H substituent at the Cc lead only mononuclear complexes or salts. The last part of the thesis (Chapter 5) deals on the capacity of the novel carboranylphosphinate ligand to bind onto the surface of magnetic nanoparticles (MNPs) via coordination to the iron atoms as a phosphinate bidentated bridging ligand (1-MNPs), and provides an understanding of how the environment influences on the strength of this bond. Of particular relevance is what refers to the stability of 1-MNPs before and after sterilization under autoclave conditions. Biological studies confirmed the uptake of 1-MNPs by the cultured cells (hCMEC/D3 and A172) and the presence of the m-carboranylphosphinate in dried-cells samples. Quantification of 1-MNPs uptake by cells displayed that glioblastoma A172 cells presented larger cellular iron contents than brain endothelial (hCMEC/D3) cells. In terms of drug safety, we have shown that the systemic administration of the 1-MNPs nanohybrids does not show major signs of toxicity in mice, supporting its potential translation into the biomedical setting.

This chapter deals with the applications of gold nanoparticle in cancer and various strategies to target cancer cells by using gold nanoparticles. They are in great demand for biomedical applications such as DNA/Protein detection, bimolecular regulators, cell imaging and cancer cell diagnostics. The ability to tune the surface of the particle provides access to cell –specific targeting and controlled drug release. Depending on their size, shape, degree of aggregation, and local environment, gold nanoparticles can appear red, blue, or other colors. The novel drug delivery systems offer the opportunity to improve poor solubility, limited stability, bio distribution, and pharmacokinetics of drug as well as offering the potential ability to target specific tissues and cell types. The multifunctional gold nanoparticles are attractive organic –inorganic hybrid material composed of an inorganic metallic gold core surrounded by an organic or bimolecular monolayer they provide desirable attributes for the creation of drug delivery in cancer.

This chapter deals with the applications of gold nanoparticle in cancer and various strategies to target cancer cells by using gold nanoparticles. They are in great demand for biomedical applications such as DNA/Protein detection, bimolecular regulators, cell imaging and cancer cell diagnostics. The ability to tune the surface of the particle provides access to cell –specific targeting and controlled drug release. Depending on their size, shape, degree of aggregation, and local environment, gold nanoparticles can appear red, blue, or other colors. The novel drug delivery systems offer the opportunity to improve poor solubility, limited stability, bio distribution, and pharmacokinetics of drug as well as offering the potential ability to target specific tissues and cell types. The multifunctional gold nanoparticles are attractive organic –inorganic hybrid material composed of an inorganic metallic gold core surrounded by an organic or bimolecular monolayer they provide desirable attributes for the creation of drug delivery in cancer.

Spinel ferrites are a widely investigated and applied class of materials with a cubic spinel lattice structure. Their unique multifunctional properties (magnetic characteristics, tunable shape/size, large number of active surface sites, high values of specific surface area, good chemical stability, and possibilities for enhancing properties through surface modification) influenced by the synthesis procedure make them attractive for biomedical applications as magnetic nanoparticles in drug delivery to a set target, magnetic hyperthermia, tissue engineering, magnetic extraction of biological components and magnetic diagnostics. In this review, we give an overview of up-to-date synthesis procedures for obtaining magnetic spinel nanoparticles and nanocomposites with optimal properties for biomedical applications.

Integration of nanotechnology and biomedicine has offered great opportunities for the development of nanoscaled therapeutic platforms. Amongst various nanocarriers, mesoporous silica nanoparticles (MSNs) is one of the most developed and promising inorganic materials-based drug delivery system for clinical translations due to their simple composition and nanoporous structure. MSNs possess unique structural features, for example, well-defined morphology, large surface areas, uniform size, controllable structure, flexible pore volume, tunable pore sizes, extraordinarily high loading efficiency, and excellent biocompatibility. Progress in structure control and functionalization may endow MSNs with functionalities that enable medical applications of these integrated nanoparticles such as molecularly targeted drug delivery, multicomponent synergistic therapy, in vivo imaging and therapeutic capability, on-demand/stimuli-responsive drug release, etc. In this chapter, the authors overview MSNs' characteristics and the scientific efforts developed till date involving drug delivery and biomedical applications.

Cancer remains the important cause for the mortality worldwide. In recent days, different biomedical strategies are in the limelight for the control of mortality due to cancer. As a promising strategy in cancer treatment, nano-formulations with advantages in drug delivery, health, and pharmacy are booming. The conventional nanocarrier continues, however, to suffer from low drug load efficiency, possible toxicity, unknown metabolism, and other uncertainties. To overcome these problems, carrier-free nanodrugs with desirable bioactivity were developed quickly and attracted considerable attention. In the meantime, the nanoarchitecture developed by a simple “natural” method with a multifunctional self-life has major advantages in multi-drug resistant synergistic cancer therapies and inhibition. Until now, the carrier-free nanoparticles for tumour therapy, phototherapy, chemotherapy, diagnostics, and synergistic therapy have made significant progress. In this review, the authors provide an integrated and detailed review of recent literature on nanodrug delivery systems composed of several active agents.

Multifunctional nanocomposites have an enormous scientific and practical future in medicine, especially in biomedical imaging and targeted delivery. Multifunctional composite nanodevices (CND) possess chemical and physical properties of all components, while interactions with the environment of the nanoparticle are dominated by the contact surface of the host molecule. Thus, if the surface is dominated by the organic component of a nano-sized organic-inorganic composite particle, an inorganic particle property can be manipulated in a biologic environment as if it belonged to an organic macromolecule. Composition, charge, and size of are critical in determining nanoparticle trafficking and uptake by organs, and therefore this knowledge is crucial for the development of cancer imaging and therapies. Specific biokinetics and biodistribution then can be influenced by correctly selecting size, and modifying surface characteristics, such as covalently attaching various targeting moieties to the surface forming biohybrids, regulating the surface charge, etc. Dendrimer nanocomposites are recently developed nearly monodisperse hybrid nanoparticles composed of macromolecular hosts and very small, uniformly dispersed inorganic guest domains combining desirable properties of the components. The surface groups control the interaction of these nanodevices with the biological environment. As a result of various synthetic options, the interior and/or the exterior of the host can be cationic, anionic, or non-ionic, depending on their termini and interior functionalities and the pH, and may involve multiple targeting moieties. We have synthesized gold/dendrimer nanocomposites to carry payload radiation and/or diagnostic moiety to specific targets. We examined the biodistribution of the templates and the corresponding gold/dendrimer nanocomposites. We employed the same dendrimer template and systematically varied the size, the surface charge and the composition. Biodistribution of {Au} gold/dendrimer nanodevices of various size (5, 12 and 22 nm) and surface charge (positive, negative) was investigated in mice models (B16 melanoma and DU145 human prostate cancer). Isotope neutron activation analysis (INAA) was used to measure the presence of Au(0) in the tissue sample. All {Au} gold/dendrimer-nanocomposites were assayed for their quantitative short-term (1hr), intermediate (1 day) and long-term (4 days) biodistribution throughout organs for clinical toxicity. Delivery of radiation dose was achieved by radioactive {198Au} composites in a mice model. We have shown that modulating surface charge and composition will greatly change the biodistribution characteristics of the nanodevices. Rigorous testing of the principles that govern nanoparticle interactions with the complex environment of biological systems will be critical for an understanding of how these nanodevices will behave in vivo.