Showing papers on "Nanobiotechnology published in 2017"

Advancement of the Emerging Field of RNA Nanotechnology.

Abstract: The field of RNA nanotechnology has advanced rapidly during the past decade. A variety of programmable RNA nanoparticles with defined shape, size, and stoichiometry have been developed for diverse applications in nanobiotechnology. The rising popularity of RNA nanoparticles is due to a number of factors: (1) removing the concern of RNA degradation in vitro and in vivo by introducing chemical modification into nucleotides without significant alteration of the RNA property in folding and self-assembly; (2) confirming the concept that RNA displays very high thermodynamic stability and is suitable for in vivo trafficking and other applications; (3) obtaining the knowledge to tune the immunogenic properties of synthetic RNA constructs for in vivo applications; (4) increased understanding of the 4D structure and intermolecular interaction of RNA molecules; (5) developing methods to control shape, size, and stoichiometry of RNA nanoparticles; (6) increasing knowledge of regulation and processing functions of RNA...

Biomedical applications of nanotechnology.

Abstract: The ability to investigate substances at the molecular level has boosted the search for materials with outstanding properties for use in medicine. The application of these novel materials has generated the new research field of nanobiotechnology, which plays a central role in disease diagnosis, drug design and delivery, and implants. In this review, we provide an overview of the use of metallic and metal oxide nanoparticles, carbon-nanotubes, liposomes, and nanopatterned flat surfaces for specific biomedical applications. The chemical and physical properties of the surface of these materials allow their use in diagnosis, biosensing and bioimaging devices, drug delivery systems, and bone substitute implants. The toxicology of these particles is also discussed in the light of a new field referred to as nanotoxicology that studies the surface effects emerging from nanostructured materials.

Triplex DNA Nanostructures: From Basic Properties to Applications.

Abstract: Triplex nucleic acids have recently attracted interest as part of the rich "toolbox" of structures used to develop DNA-based nanostructures and materials. This Review addresses the use of DNA triplexes to assemble sensing platforms and molecular switches. Furthermore, the pH-induced, switchable assembly and dissociation of triplex-DNA-bridged nanostructures are presented. Specifically, the aggregation/deaggregation of nanoparticles, the reversible oligomerization of origami tiles and DNA circles, and the use of triplex DNA structures as functional units for the assembly of pH-responsive systems and materials are described. Examples include semiconductor-loaded DNA-stabilized microcapsules, DNA-functionalized dye-loaded metal-organic frameworks (MOFs), and the pH-induced release of the loads. Furthermore, the design of stimuli-responsive DNA-based hydrogels undergoing reversible pH-induced hydrogel-to-solution transitions using triplex nucleic acids is introduced, and the use of triplex DNA to assemble shape-memory hydrogels is discussed. An outlook for possible future applications of triplex nucleic acids is also provided.

In Situ Characterization of Protein Adsorption onto Nanoparticles by Fluorescence Correlation Spectroscopy

Abstract: ConspectusNanotechnology holds great promise for applications in many fields including biology and medicine. Unfortunately, the processes occurring at the interface between nanomaterials and living systems are exceedingly complex and not yet well understood, which has significantly hampered the realization of many nanobiotechnology applications. Whenever nanoparticles (NPs) are incorporated by a living organism, a protein adsorption layer, also known as the “protein corona”, forms on the NP surface. Accordingly, living organisms interact with protein-coated rather than bare NPs, and their biological responses depend on the nature of the protein corona. In recent years, a wide variety of biophysical techniques have been employed to elucidate mechanistic aspects of NP–protein interactions. In most studies, NPs are immersed in protein or biofluid (e.g., blood serum) solutions and then separated from the liquid for analysis. Because this approach may modify the composition and structure of the protein corona,...

Biomolecular engineering for nanobio/bionanotechnology

Abstract: Biomolecular engineering can be used to purposefully manipulate biomolecules, such as peptides, proteins, nucleic acids and lipids, within the framework of the relations among their structures, functions and properties, as well as their applicability to such areas as developing novel biomaterials, biosensing, bioimaging, and clinical diagnostics and therapeutics. Nanotechnology can also be used to design and tune the sizes, shapes, properties and functionality of nanomaterials. As such, there are considerable overlaps between nanotechnology and biomolecular engineering, in that both are concerned with the structure and behavior of materials on the nanometer scale or smaller. Therefore, in combination with nanotechnology, biomolecular engineering is expected to open up new fields of nanobio/bionanotechnology and to contribute to the development of novel nanobiomaterials, nanobiodevices and nanobiosystems. This review highlights recent studies using engineered biological molecules (e.g., oligonucleotides, peptides, proteins, enzymes, polysaccharides, lipids, biological cofactors and ligands) combined with functional nanomaterials in nanobio/bionanotechnology applications, including therapeutics, diagnostics, biosensing, bioanalysis and biocatalysts. Furthermore, this review focuses on five areas of recent advances in biomolecular engineering: (a) nucleic acid engineering, (b) gene engineering, (c) protein engineering, (d) chemical and enzymatic conjugation technologies, and (e) linker engineering. Precisely engineered nanobiomaterials, nanobiodevices and nanobiosystems are anticipated to emerge as next-generation platforms for bioelectronics, biosensors, biocatalysts, molecular imaging modalities, biological actuators, and biomedical applications.

Synthesis of Nanoparticles by Green Synthesis Method

Abstract: As an emphasis on the synergistic interaction of nanotechnology and nanobiotechnology, nanoparticles need to develop environmentally benign technologies in the synthesis of bio-synthesis and nanomaterialsMicroorganisms, plants and fungi can be used as biodegradable agent material inthis field work Thus, it was possible to develop a simple, fast and green method for the synthesis of nanoparticles Various strategies are used for the synthesis of nanoparticles Traditionally, physicochemical techniques have increased environmental con-cerns due to the reduction of metal ions followed by surface modification, toxiccompounds added for stability, and dangerous byproducts formed At the time of nanoparticle synthesis by adding chemical and physical methods at high temperature and pressure, reducing and stabilizing agents; nanoparticle synthesis by biological methods; room temperature and pres-sure, reducing and stabilizing agents are needed Green synthesis method; provides a faster metallic nanoparticle production by offering an environmentally friendly, simple, economi-cal and reproducible approach Given the wide range of applications of metallic nanoparticles produced, biological methods play a major role in the synthesis of metallic nanoparticles

Modular and Orthogonal Post-PEGylation Surface Modifications by Insertion Enabling Penta-functional Ultrasmall Organic-Silica Hybrid Nanoparticles

Abstract: Multifunctional nanoparticles (NPs) combining different functional components into a single NP platform are of great interest in the fields of nanobiotechnology and nanomedicine. Here, we report a versatile surface modification approach to modularly and orthogonally functionalize Cornell prime dots (C′ dots), ultrasmall sub-10 nm PEGylated fluorescent core–shell silica nanoparticles that have been translated into the clinic, with up to four types of different functional ligands on the NP surface. It enables the synthesis of penta-functional C′ dots integrating a variety of properties into a single NP, i.e., fluorescence detection, specific cell targeting, radioisotope chelating/labeling, ratiometric pH sensing, and drug delivery, while the overall NP size remains below 7 nm. This is achieved by taking advantage of the fact that the PEG layer of C′ dots is penetrable to small molecules. Amine- and/or thiol-functionalized silane molecules can be inserted between PEG chains and onto the silica surface of C′ ...

Green Synthesized Gold Nanoparticles for Future Biomedical Applications

Abstract: Nanobiotechnology is an emerging field of biological and engineering sciences. The design and development of green chemistry approach for the synthesis of biocompatible nanoparticles is always better selection due to eco-friendliness. The green chemistry approach for the synthesis of metal nanoparticles has several advantages (simple, safer, energy efficient, fast, mostly one-pot processes, inexpensive, and less toxic routes toward synthesis) over conventional synthetic procedures. Among various biologically synthesized metal nanoparticles, noble nanoparticles (gold, silver and platinum) especially gold nanoparticles (AuNPs) are exceptionally attractive in biomedical application due to presence of unusual physicochemical properties, ease of synthesis and surface modification in the nanoscale range, biocompatibility, and several other advantages. Recently, several researchers including our group have intensely focused to explore the green synthesis and potential applications of AuNPs in biology and medicine. In this chapter, we discuss about the (i) synthesis of AuNPs using rational utilization of various bioresources, (ii) their prospective applications toward various disease therapy, (iii) in vitro and in vivo toxicity, (iv) biodistribution studies, and (v) future challenges and opportunities.

Recent advances in peptide nucleic acid for cancer bionanotechnology.

Abstract: Peptide nucleic acid (PNA) is an oligomer, in which the phosphate backbone has been replaced by a pseudopeptide backbone that is meant to mimic DNA. Peptide nucleic acids are of the utmost importance in the biomedical field because of their ability to hybridize with neutral nucleic acids and their special chemical and biological properties. In recent years, PNAs have emerged in nanobiotechnology for cancer diagnosis and therapy due to their high affinity and sequence selectivity toward corresponding DNA and RNA. In this review, we summarize the recent progresses that have been made in cancer detection and therapy with PNA biotechnology. In addition, we emphasize nanoparticle PNA-based strategies for the efficient delivery of drugs in anticancer therapies.

Gold Nanoparticles in Biomedical Applications

Abstract: This book discusses fabrication of functionalized gold nanoparticles (GNPs) and multifunctional nanocomposites, their optical properties, and applications in biological studies This is the very first book of its kind to comprehensively discuss published data on in vitro and in vivo biodistribution, toxicity, and uptake of GNP by mammalian cells providing a systematization of data over the GNP types and parameters, their surface functionalization, animal and cell models As distinct from other related books, Gold Nanoparticles in Biomedical Applications discusses the immunological properties of GNPs and summarizes their applications as an antigen carrier and adjuvant in immunization for the preparation of antibodies in vivo Although the potential of GNPs in nanobiotechnology has been recognized for the past decade, new insights into the unique properties of multifunctional nanostructures have recently emerged With these developments in mind, this book unites ground breaking experimental data with a discussion of hybrid nanoparticle systems that combine different nanomaterials to create multifunctional structures These novel hybrids constitute the material basis of theranostics, bringing together the advanced properties of functionalized GNPs and composites into a single multifunctional nanostructure with simultaneous diagnostic and therapeutic functions Such nanohybrids can be physically and chemically tailored for a particular organ, disease, and patient thus making personalized medicine available

Biosynthesis of silver nanoparticles by endophytic fungi: Its mechanism, characterization techniques and antimicrobial potential

Abstract: Nanotechnology has rapidly developed as an important field of modern research, generating most promising applications in electronics and medicine. It involves different approaches for the synthesis and application of nanoparticles having dimension smaller than 100 nm. Nanoparticles are the fundamental building blocks for preparing many nanostructured materials and devices. Therefore, there is an enormous interest in developing safe, cost effective and ecofriendly techniques for synthesis of nanoparticles. Biological synthesis has emerged as an attractive alternative to overcome the side effects accompanied with physical and chemical methods of synthesis. This led to the development of new branch of nanotechnology called “green nanotechnology” or “nanobiotechnology” which combines biological principles with physical and chemical procedures to generate eco-friendly nano-sized particles with specific functions. Various biological entities could be employed for the biosynthesis of nanoparticles including plant, algae, fungi, yeast, bacteria and viruses. Recently, much attention has been given on exploring fungi as potent biofactories for synthesis of silver nanoparticles since they possess numerous bioactive properties which find variety of applications in the field of biomedicine. Its use in the form of effective antimicrobial agent and disinfectant is known since time immemorial. The present chapter emphasize on the richness of endophytic fungal diversity and their role in biosynthesis of silver nanoparticles. It gives detailed overview about the mechanism of synthesis, characterization techniques involved in analysis of silver nanoparticles and biomedical application of silver nanoparticles with special reference to their antimicrobial potential. Key words: Nanobiotechnology, silver nanoparticles, endophytic fungi, antimicrobial potential, eco-friendly.

In Vivo Delivery of Nanoparticles into Plant Leaves

Abstract: Plant nanobiotechnology is an interdisciplinary field at the interface of nanotechnology and plant biology that aims to utilize nanomaterials as tools to study, augment or impart novel plant functions. The delivery of nanoparticles to plants in vivo is a key initial step to investigate plant nanoparticle interactions and the impact of nanoparticles on plant function. Quantum dots are smaller than plant cell wall pores, have versatile surface chemistry, bright fluorescence and do not photobleach, making them ideal for the study of nanoparticle uptake, transport, and distribution in plants by widely available confocal microscopy tools. Herein, we describe three different methods for quantum dot delivery into leaves of living plants: leaf lamina infiltration, whole shoot vacuum infiltration, and root to leaf translocation. These methods can be potentially extended to other nanoparticles, including nanosensors and drug delivery nanoparticles. © 2017 by John Wiley & Sons, Inc.

A Biomimetic Escape Strategy for Cytoplasm Invasion by Synthetic Particles

Abstract: The translocation of nanomaterials or complex delivery systems into the cytosol is a major challenge in nanobiotechnology. After receptor-mediated endocytosis, most nanomaterials are sequestered and undergo degradation, therapy inactivation, or exocytosis. Herein we explore a novel surface particle coating made of adsorbed carbon nanotubes that provides coated materials with new properties that reproduce the viral cell-invasive mechanisms, namely, receptor-mediated endocytosis, endolysosomal escape, and cytosolic particle release preserving cell viability. This novel biomimetic coating design will enable the intracytoplasmic delivery of many different functional materials endowed with therapeutic, magnetic, optical, or catalytic functionalities, thus opening the door to a wide array of chemical and physical processes within the cytosolic or nuclear domains, and supporting new developments in the biotechnological, pharmaceutical, and biomedical industries.

Bacterial Synthesis and Applications of Nanoparticles

Abstract: Nanoparticles synthesis is the real division in the area of relevant Nanotechnology and Nanoscience. As of late, the merging amongst nanotechnology and science has made the new field of Nanobiotechnology that joins the utilization of natural elements, for example, algae, microscopic organisms, parasites, infections, yeasts and plants in various biophysical and biochemical procedures. The natural combination forms have a critical prospective to support nanoparticles generation without the utilization of brutal, harmful and costly chemicals usually utilized as a part of ordinary physical and substance forms. Combination of nanoparticles (NPs) utilizing microscopic organisms has risen as quickly creating research range in nanotechnology over the globe. The procedures of NPs combination result with required shapes and controlled sizes, quick and clean. These days, a variety of nanoparticles with very much characterized synthetic organization, size and morphology have been combined by utilizing distinctive microorganisms and their applications in numerous mechanical fields have been investigated. The uses of these biosynthesized nanoparticles in a wide range of potential zones are exhibited including focused on targeted drug passage, malignancy treatment and DNA investigation, biosensors and magnetic resonance imaging (MRI). The consumption of microorganisms for nanoparticles synthesis is a genuinely unique range of examination with extensive prospective for more improvement.

Designing synthetic RNA for delivery by nanoparticles.

Abstract: The rapid development of synthetic biology and nanobiotechnology has led to the construction of various synthetic RNA nanoparticles of different functionalities and potential applications. As they occur naturally, nucleic acids are an attractive construction material for biocompatible nanoscaffold and nanomachine design. In this review, we provide an overview of the types of RNA and nucleic acid's nanoparticle design, with the focus on relevant nanostructures utilized for gene-expression regulation in cellular models. Structural analysis and modeling is addressed along with the tools available for RNA structural prediction. The functionalization of RNA-based nanoparticles leading to prospective applications of such constructs in potential therapies is shown. The route from the nanoparticle design and modeling through synthesis and functionalization to cellular application is also described. For a better understanding of the fate of targeted RNA after delivery, an overview of RNA processing inside the cell is also provided.

Nanoscale hybrid systems based on carbon nanotubes for biological sensing and control.

Abstract: This paper provides a concise review on the recent development of nanoscale hybrid systems based on carbon nanotubes (CNTs) for biological sensing and control. CNT-based hybrid systems have been intensively studied for versatile applications of biological interfaces such as sensing, cell therapy and tissue regeneration. Recent advances in nanobiotechnology not only enable the fabrication of highly sensitive biosensors at nanoscale but also allow the applications in the controls of cell growth and differentiation. This review describes the fabrication methods of such CNT-based hybrid systems and their applications in biosensing and cell controls.

Synthesis and Optical Properties of Highly Stabilized Peptide-Coated Silver Nanoparticles

Abstract: The interaction between peptide and gold nanoparticle surfaces has been increasingly of interest for bionanotechnology applications. To fully understand how to control such interactions, we have studied the optical properties of peptide-modified gold nanoparticles. However, the impacts of peptide binding motif upon the surface characteristics and physicochemical properties of nanoparticles remain poorly understood. Here, we have prepared sodium citrate-stabilized gold nanoparticles and coated with peptide IVD (ID3). These nanomaterials were characterized by UV-visible, transmission electron microscopy (TEM), and z-potential measurement. The results indicate that gold-peptide interface is generated using ID3 peptide and suggested that the reactivity of peptide is governed by the conformation of the bound peptide on the nanoparticle surface. The peptide-nanoparticle interactions could potentially be used to make specific functionality into the peptide capped nanomaterials.

Does nanobiotechnology create new tools to combat microorganisms

Abstract: Abstract Antimicrobial resistance is still a crucial global problem related to the overuse of antibiotics and natural microorganism capability for rapid horizontal evolution. Even new generations of drugs are not able to overcome bacterial defence mechanisms. A novel solution for this immense medical challenge can be nanomaterials. Researchers indicate that modern nanoforms can effectively support and perhaps in the long-term replace traditional bactericidal agents. Because of their unique physicochemical properties, nanotechnology products can exert multiple actions against bacteria, which might be efficient against even multidrug-resistant pathogens. In this review, we discuss the documented achievements and concerns associated with broad potential applications of nanoforms in the fight against microorganisms.

Nanobiotechnology for Breast Cancer Treatment

Abstract: Despite many technological breakthroughs, even the best breast cancer treatments available today are not 100% effective. Chemotherapy has improved, but many drugs still do not reach the tumor site at effective doses and are often associated with high systemic toxicity and poor pharmacokinetics. Moreover, for many malignancies, diagnosis is obtainable only in metastatic stages of development, reducing the overall effectiveness of treatment. The choice of available treatments depends on tumor characteristics such as biomarkers, tumor size, metastatic disease, ligands, and antigen or endocrine receptor expression. Combined with surgical resection, chemotherapy and radiation remain the first line of treatment for patients with cancer. Even with these treatments, however, cancer continues to have high fatality rates and current therapeutic modalities have yet to significantly improve the often dismal prognosis of this disease. Nanotechnology is a highly focused approach, which may provide more effective and less toxic treatment when compared to chemotherapy. This area of research has emerged as cancer treatment in the form of new drugs and has reached promising results in preclinical and clinical trials proving its value as a potential tumor therapy.

Biophysical and electrochemical properties of Self-assembled noncovalent SWNT/DNA hybrid and electroactive nanostructure

Abstract: DNA self-assembled hybrid nanostructures are widely used in recent research in nanobiotechnology. Combination of DNA with carbon based nanoparticles such as single-walled carbon nanotube (SWNT), multi-walled carbon nanotube (MWNT) and carbon quantum dot were applied in important biological applications. Many examples of biosensors, nanowires and nanoelectronic devices, nanomachine and drug delivery systems are fabricated by these hybrid nanostructures. In this study, a new hybrid nanostructure has been fabricated by noncovalent interactions between single or double stranded DNA and SWNT nanoparticles and biophysical properties of these structures were studied comparatively. Biophysical properties of hybrid nanostructures studied by circular dichroism, UV–vis and fluorescence spectroscopy techniques. Also, electrochemical properties studied by cyclic voltammetry, linear sweep voltammetry, square wave voltammetry, choronoamperometry and impedance spectroscopy (EIS). Results revealed that the biophysical and electrochemical properties of SWNT/DNA hybrid nanostructures were different compare to ss-DNA, ds-DNA and SWNT singly. Circular dichroism results showed that ss-DNA wrapped around the nanotubes through π-π stacking interactions. The results indicated that after adding SWNT to ss-DNA and ds-DNA intensity of CD and UV–vis spectrum peaks were decreased. Electrochemical experiments indicated that the modification of single-walled carbon nanotubes by ss-DNA improves the electron transfer rate of hybrid nanostructures. It was demonstrated SWNT/DNA hybrid nanostructures should be a good electroactive nanostructure that can be used for electrochemical detection or sensing.

Solid-Binding Peptides in Biomedicine.

Abstract: Some peptides are able to bind to inorganic materials such as silica and gold. Over the past decade, Solid-binding peptides (SBPs) have been used increasingly as molecular building blocks in nanobiotechnology. These peptides show selectivity and bind with high affinity to a diverse range of inorganic surfaces e.g. metals, metal oxides, metal compounds, magnetic materials, semiconductors, carbon materials, polymers and minerals. They can be used in applications such as protein purification and synthesis, assembly and the functionalization of nanomaterials. They offer simple and versatile bioconjugation methods that can increase biocompatibility and also direct the immobilization and orientation of nanoscale entities onto solid supports without impeding their functionality. SBPs have been employed in numerous nanobiotechnological applications such as the controlled synthesis of nanomaterials and nanostructures, formation of hybrid biomaterials, immobilization of functional proteins and improved nanomaterial biocompatibility. With advances in nanotechnology, a multitude of novel nanomaterials have been designed and synthesized for diagnostic and therapeutic applications. New approaches have been developed recently to exert a greater control over bioconjugation and eventually, over the optimal and functional display of biomolecules on the surfaces of many types of solid materials. In this chapter we describe SBPs and highlight some selected examples of their potential applications in biomedicine.

Nanobiosensors, as a Next-Generation Diagnostic Device for Quality & Safety of Food and Dairy Product

Abstract: Nanotechnology and biotechnology are a sole combination and generate a new advanced discipline: nanobiotechnology. It includes the application of the tools and processes of nanotechnology to study and manipulate biological systems. Nanobiosensor is an advanced, analytical technique designed and developed by nanotechnology and biotechnological applications. They have remarkable benefits with cost-effective, high selectivity, specificity, more rapid, robust, and sensitive quantitative techniques for field analysis capability. These techniques have proved to be the best tools to ensure food and dairy product quality and safety. This chapter focuses on the potential role of nanomaterials (gold, magnetic, carbon nanotube, silver nanoparticles, etc.), which are currently being used in various nanobiosensors to find various chemical adulterants, different toxins, and harmful pathogens. Analysis of food and dairy products for adulterants, such as starch, urea, hydrogen peroxide, neutralizer, detergents, boric acid, melamine, mycotoxins, and bacteria, is performed. Various nanobiosensor used for this purpose are nanowire biosensors, ion channel biosensor, cantilever biosensor, and optical biosensor.

Using Planar Phi29 pRNA Three-Way Junction to Control Size and Shape of RNA Nanoparticles for Biodistribution Profiling in Mice

Abstract: RNA is rapidly emerging as a versatile building block for nanoparticle assembly due to its simplicity in base pairing, while exhibiting diversity in function such as enzymatic activity similar to some proteins. Recent advances in RNA nanotechnology have generated significant interests in applying RNA nanoparticles for various applications in nanotechnology and nanomedicine. In particular, assessing the effect of size and shape on cell entry and intracellular trafficking as well as in vivo biodistribution of nanoparticles is challenging due to the lack of nanoparticles rich in structure while varying in size and shape. RNA nanotechnology exemplified by the packaging RNA (pRNA) of bacteriophage phi29 DNA packaging motor has provided a different prospect in nanoparticle designs. Of note, there is a robust three-way junction (3WJ) motif in pRNA which can serve as an adaptable scaffold to construct thermodynamically stable 2D planar and 3D globular RNA architectures with tunable shapes and sizes, and harboring various targeting, therapeutic, and imaging modules. This chapter focuses on the methods for constructing pRNA-3WJ based nanoparticles with controllable sizes and shapes, and assessment of their biodistribution profiles in cancer mouse models after systemic injection and ocular mouse models following subconjunctival injection.

Silver nanoparticles: A new Era of nanobiotechnology

Abstract: Nanotechnology is a fast emerging field in physics, chemistry as well as in biology. In view of the tremendous applications of nanotechnology, scientists are in flick to carry out research in this vital discipline. Chemists are highly interested in synthesizing nanoparticles of different dimensions employing many of the precious metals. Now a days scientist have started the exploitation of bio-based synthesis of nano-particles using leaf extracts and microorganisms. The development of eco-friendly procedures for the metal nanoparticles synthesis through biological process is evolving into an important branch of nanobiotechnology. Generally, nanoparticles are synthesized by chemical and physical methods, which are not eco-friendly so it is necessity to synthesized nanoparticles using plant extracts or from the plant source. Nanotechnology is gaining tremendous impetus in the present century due to its capability of modulating metals into their nanosize, which drastically changes the chemical, physical and optical properties of metals. Metallic silver in the form of silver nanoparticles has made a remarkable comeback as a potential antimicrobial agent.

Development of Diverse Size and Shape RNA Nanoparticles and Investigation of their Physicochemical Properties for Optimized Drug Delivery

Abstract: OF DISSERTATION DEVELOPMENT OF DIVERSE SIZE AND SHAPE RNA NANOPARTICLES AND INVESTIGATION OF THEIR PHYSICOCHEMICAL PROPERTIES FOR OPTIMIZED DRUG DELIVERY RNA nanotechnology is an emerging field that holds great promise for advancing drug delivery and materials science. Recently, RNA nanoparticles have seen increased use as an in vivo delivery system. RNA was once thought to have little potential for in vivo use due to biological and thermodynamic stability issues. However, these issues have been solved by: (1) Finding of a thermodynamically stable three-way junction (3WJ) motif; (2) Chemical modifications to RNA confer enzymatic stability in vivo; and (3) the finding that RNA nanoparticles exhibit low immunogenicity in vivo. In vivo biodistribution and pharmacokinetics are affected by the physicochemical properties, such as size, shape, stability, and surface chemistry/properties, of the nanoparticles being delivered. RNA has an inherent advantage for nanoparticle construction as each of these properties can be finely tuned. The focus of this study is as follows: (1) Construction of diverse size and shape RNA nanoparticles with tunable physicochemical properties; (2) Investigation of the effect that size, shape, and nanoparticle properties have on in vivo biodistribution; (3) Development of drug encapsulation and release mechanism utilizing RNA nanotechnology; and (4) Establishment of large-scale synthesis and purification methods of RNA nanoparticles. In (1), RNA triangle, square, and pentagon shaped nanoparticles were constructed using the phi29 pRNA-3WJ as a core motif. Square nanoparticles were constructed with sizes of 5, 10, and 20 nanometers. The RNA polygons were characterized by AFM to demonstrate formation of their predicted geometry per molecular models. Furthermore, the properties of RNA polygons were tuned both thermodynamically and chemically by substitution of nucleic acid type used during nanoparticle assembly. In (2), the biodistribution of RNA nanosquares of diverse sizes and RNA polygons of diverse shapes were investigated using tumor models in nude mice. It was found that increasing the size of the nanosquares led to prolonged circulation time in vivo and higher apparent accumulation in the tumor. However, it was observed that changing of shape had little effect on biodistribution. Furthermore, the effect of the hydrophobicity on RNA nanoparticles biodistribution was examined in mouse models. It was found that incorporation of hydrophobic ligands into RNA nanoparticles causes non-specific accumulation in healthy organs, while incorporation of hydrophilic ligands does not. Lower accumulation in vital organs of hydrophobic chemicals was observed after conjugation to RNA nanoparticles, suggesting RNA has the property to solubilize hydrophobic chemicals and reduce accumulation and toxicity in vital organs. In (3), a 3D RNA nanoprism was constructed to encapsulate a small molecule fluorophore acting as a model drug. The fluorophore was held inside the nanoprism by binding to an RNA aptamer. The ability of the stable frame of the nanoprism to protect the fragile aptamer inside was evidenced by a doubling of the fluorescent half-life in a degrading environment. In (4), a method for large-scale in vitro synthesis and purification of RNA nanoparticles was devised using rolling circle transcription (RCT). A novel method for preparing circular double stranded DNA was developed, overcoming current challenges in the RCT procedure. RCT produced more than 5 times more RNA nanoparticles than traditional run-off transcription, as monitored by gel electrophoresis and fluorescence monitoring. Finally, large-scale purification methods using rate-zonal and equilibrium density gradient ultracentrifugation, as well as gel electrophoresis column, were developed.

A synthetic getaway biomimetic strategy for cytoplasm particle invasion

Abstract: The translocation of nanomaterials or complex delivery systems into the cytosol is a main challenge in nanobiotechnology. After receptor-mediated endocytosis, most nanomaterials are sequestered undergoing degradation, therapy inactivation or exocytosis. Here we explore a novel surface particle-coating made of adsorbed carbon nanotubes that provides coated materials with new properties that reproduce the viral cell invasive mechanisms, namely: receptor mediated endocytosis, endo-lysosomal escape and cytosolic particle release preserving intact cell viability. This novel biomimetic coating design will enable the intracytoplasmic delivery of many different functional materials endowed with therapeutic, magnetic, optical or catalytic functionalities thus, opening the door to a wide array of chemical and physical processes within the cytosolic or nuclear domains, and supporting the generation of new developments in the biotechnological, pharmaceutical and biomedical industries.

Bacterial Synthesis and Applications of Nanoparticles

Abstract: Nanoparticles synthesis is the real division in the area of relevant Nanotechnology and Nanoscience. As of late, the merging amongst nanotechnology and science has made the new field of Nanobiotechnology that joins the utilization of natural elements, for example, algae, microscopic organisms, parasites, infections, yeasts and plants in various biophysical and biochemical procedures. The natural combination forms have a critical prospective to support nanoparticles generation without the utilization of brutal, harmful and costly chemicals usually utilized as a part of ordinary physical and substance forms. Combination of nanoparticles (NPs) utilizing microscopic organisms has risen as quickly creating research range in nanotechnology over the globe. The procedures of NPs combination result with required shapes and controlled sizes, quick and clean. These days, a variety of nanoparticles with very much characterized synthetic organization, size and morphology have been combined by utilizing distinctive microorganisms and their applications in numerous mechanical fields have been investigated. The uses of these biosynthesized nanoparticles in a wide range of potential zones are exhibited including focused on targeted drug passage, malignancy treatment and DNA investigation, biosensors and magnetic resonance imaging (MRI). The consumption of microorganisms for nanoparticles synthesis is a genuinely unique range of examination with extensive prospective for more improvement.