Strategies to assemble therapeutic and imaging molecules into inorganic nanocarriers

Inorganic nanocarriers are potent candidates for delivering conventional anticancer drugs, nucleic acid-based therapeutics, and imaging agents, influencing their blood half-lives, tumor targetability, and bioactivity. In addition to the high surface area-to-volume ratio, they exhibit excellent scalability in synthesis, controllable shape and size, facile surface modification, inertness, stability, and unique optical and magnetic properties. However, only a limited number of inorganic nanocarriers have been so far approved for clinical applications due to burst drug release, poor target specificity, and toxicity. To overcome these barriers, understanding the principles involved in loading therapeutic and imaging molecules into these nanoparticles (NPs) and the strategies employed in enhancing sustainability and targetability of the resultant complexes and ensuring the release of the payloads in extracellular and intracellular compartments of the target site is of paramount importance. Therefore, we will shed light on various loading mechanisms harnessed for different inorganic NPs, particularly involving physical entrapment into porous/hollow nanostructures, ionic interactions with native and surface-modified NPs, covalent bonding to surface-functionalized nanomaterials, hydrophobic binding, affinity-based interactions, and intercalation through co-precipitation or anion exchange reaction.     

Fluorescent Polymer Nanoparticles Based on Dyes: Seeking Brighter Tools for Bioimaging

Speed, resolution and sensitivity of today's fluorescence bioimaging can be drastically improved by fluorescent nanoparticles (NPs) that are many‐fold brighter than organic dyes and fluorescent proteins. While the field is currently dominated by inorganic NPs, notably quantum dots (QDs), fluorescent polymer NPs encapsulating large quantities of dyes (dye‐loaded NPs) have emerged recently as an attractive alternative. These new nanomaterials, inspired from the fields of polymeric drug delivery vehicles and advanced fluorophores, can combine superior brightness with biodegradability and low toxicity. Here, we describe the strategies for synthesis of dye‐loaded polymer NPs by emulsion polymerization and assembly of pre‐formed polymers. Superior brightness requires strong dye loading without aggregation‐caused quenching (ACQ). Only recently several strategies of dye design were proposed to overcome ACQ in polymer NPs: aggregation induced emission (AIE), dye modification with bulky side groups and use of bulky hydrophobic counterions. The resulting NPs now surpass the brightness of QDs by ≈10‐fold for a comparable size, and have started reaching the level of the brightest conjugated polymer NPs. Other properties, notably photostability, color, blinking, as well as particle size and surface chemistry are also systematically analyzed. Finally, major and emerging applications of dye‐loaded NPs for in vitro and in vivo imaging are reviewed.     

Metal nanoparticles synthesis through natural phenolic acids

For being applied in medicine as therapeutic agents, nanostructures need to be biocompatible and eco‐friendly. Plant‐derived phenolic acids have been utilised for green synthesis of metallic or metallic oxide nanoparticles (NPs). The phenolic acids play role as both reducing agents and stabilisers in the process of NPs synthesis. Many experiments have been dedicated to develop efficient green synthesis techniques for producing metal NPs. Using phenolic acids represents a reproducible, simple, profitable, and cost‐effective strategy to synthesise metal NPs. As a phytochemical for metal NPs synthesis, phenolic acids are antioxidants that represent many health benefits. However, limited studies have been dedicated to the synthesis and characterisation of NPs produced by phenolic acids. Thus, this review focused on phenolic acids mediated nanomaterial synthesis and its biomedical applications. It should be noted the mechanism of metal ion bioreduction, phenolic acids surface adsorption, characterisation, and toxicity of metal NPs made with different phenolic acids have been discussed in this review.Inspec keywords: bio‐inspired materials, organic compounds, adsorption, nanofabrication, nanoparticles, biomedical materials, nanomedicineOther keywords: toxicity, biomedical applications, antioxidants, phytochemical synthesis, reducing agents, therapeutic agents, medicine, metallic oxide nanoparticles, plant‐derived phenolic acids, natural phenolic acids, metal nanoparticles synthesis, phenolic acids surface adsorption, metal ion bioreduction, nanomaterial synthesis, efficient green synthesis techniques     

Nucleic Acids and Smart Materials: Advanced Building Blocks for Logic Systems

Logic gates can convert input signals into a defined output signal, which is the fundamental basis of computing. Inspired by molecular switching from one state to another under an external stimulus, molecular logic gates are explored extensively and recognized as an alternative to traditional silicon‐based computing. Among various building blocks of molecular logic gates, nucleic acid attracts special attention owing to its specific recognition abilities and structural features. Functional materials with unique physical and chemical properties offer significant advantages and are used in many fields. The integration of nucleic acids and functional materials is expected to bring about several new phenomena. In this Progress Report, recent progress in the construction of logic gates by combining the properties of a range of smart materials with nucleic acids is introduced. According to the structural characteristics and composition, functional materials are categorized into three classes: polymers, noble‐metal nanomaterials, and inorganic nanomaterials. Furthermore, the unsolved problems and future challenges in the construction of logic gates are discussed. It is hoped that broader interests in introducing new smart materials into the field are inspired and tangible applications for these constructs are found.     

Inorganic nanoparticles and the microbiome

Routine exposure to inorganic nanoparticles (NPs) that are incorporated into consumer products such as foods/drinks, packaging materials, pharmaceuticals, and personal care products (e.g. cosmetics, sunscreens, shampoos) occurs on a daily basis. The standard everyday use of these products facilitates interactions between the incorporated inorganic NPs, mammalian tissues (e.g. skin, gastrointestinal tract, oral cavity), and the community of microbes that resides on these tissues. Changes to the microbiome have been linked to the initiation/ progression of many diseases and there is a growing interest focused on understanding how inorganic NPs can initiate these changes. As these mechanisms are revealed and defined, it may be possible to rationally design microbiotamodulating therapies based on inorganic NPs. In this article, we will: (i) provide a background on inorganic NPs that are commonly found in consumer products such as those that incorporate titanium, zinc, silver, silica, or iron, (ii) discuss how NP properties, microbiota composition, and the physiological microenvironment can mediate the effects that inorganic NPs have on the microbiota, and (iii) highlight opportunities for inorganic NP therapies that are designed to interact with, and navigate, the microbiome.     

Water treatment via non-membrane inorganic nanoparticles/cellulose composites

Nanomaterials offer innovations in water purification technology with decreased operational and capital cost, reduced dosage, and improved pollutant selectivity. In particular, inorganic nanoparticles (NPs)/cellulose hybrid nanocomposites have attracted growing interest due to the unique properties of cellulose and high specific surface area of NPs and their pollutant selectivity. The integration with cellulose brings benefits to inorganic NPs for water treatment, including preventing agglomeration, ensuring colloidal stability, and allowing for separation by magnetic nanoparticles after purification. In this review, firstly, conventional water treatment technologies are introduced (Section 1). Following this, an overview of inorganic NPs/cellulose composites for water treatment (Section 2) is presented. Moreover, engineering of such hybrid composites is discussed (Section 3). Furthermore, water purification of inorganic NPs/cellulose through adsorption of pollutants (Section 4) and non-adsorption (catalytic, photocatalytic, and antibacterial) activities (Section 5) are highlighted. Finally, conclusions and outlook are provided (Section 6).     

Design and application of inorganic nanoparticle superstructures: current status and future challenges

Self-assembly of inorganic nanoparticles (NPs) into superstructures, which is used as a general way to integrate functional inorganic NPs into macroscale devices, has attracted much research interest. This review will summarize the recent progress and discuss future challenges of the inorganic NP superstructures. Examples include both DNA-based and polymer-based NP assemblies with controlled positioning and geometries, and quasicrystalline ordered structures from the self-assembly of binary or ternary NPs. Different from their individual NP counterparts, these self-assembled superstructures possess unique properties, such as optical chirality and dynamic structural change under an external stimulus. Due to their diversified structures and functionalities, inorganic NP superstructures have shown a wide range of promise for applications in electronic and photonic devices, such as field-effect transistors, magnetoresistive components, optical information recording, and solar cells.     

Coordination-Driven One-Step Rapid Self-Assembly Synthesis of Dual-Functional Ag@Pt Nanozyme

Realizing high-precise and adjustable regulation of engineering nanozyme is important in nanotechnology. Here, Ag@Pt nanozymes with excellent peroxidase-like and antibacterial effects are designed and synthesized by nucleic acid and metal ions coordination-driven one-step rapid self-assembly. The adjustable NA-Ag@Pt nanozyme is synthesized within 4 min using single-stranded nucleic acid as templates, and peroxidase-like enhancing FNA-Ag@Pt nanozyme is received by regulating functional nucleic acids (FNA) based on NA-Ag@Pt nanozyme. Both Ag@Pt nanozymes that are developed not only has simple and general synthesis approaches, but also can produce artificial precise adjustment and possess dual-functional. Moreover, when lead ion-specific aptamers as FNA are introduced to NA-Ag@Pt nanozyme, the Pb²⁺ aptasensor is successfully constructed by increasing electron conversion efficiency and improving the specificity of nanozyme. In addition, both nanozyme has good antibacterial properties, with ~100% and ~85% antibacterial efficiency against Escherichia coli and Staphylococcus aureus, respectively. This work provides a synthesis method of novelty dual-functional Ag@Pt nanozymes and successful application in metal ions detection and antibacterial agents.     

Antimicrobial power of biosynthesized Ag nanoparticles using refined Ginkgo biloba leaf extracts

Silver nanoparticles (Ag NPs), relative to existing antibacterial agents, are more effective, less toxic and more economical, and have shown enormous potential for the nanomedicine application. In this work, we report a ‘green’ method for the rapid and efficient synthesis of Ag NPs using Ginkgo biloba extracts as reducing agent and capping agent. The properties of Ag NPs against fungi and bacteria were investigated. The results showed that the Ginkgo biloba extracts are crucial for the preparation of uniform and monodispersed Ag NPs. The prepared Ag NPs exhibited remarkable antibacterial activities. The minimum inhibitory concentrations of Ag NPs for Escherichia coli and Pseudomonas aeruginosa were 0.044 and 0.088 μg·mL⁻¹, respectively. Moreover, Ag NPs exhibited excellent bactericidal performance against MDR-Pseudomonas aeruginosa. It was found that the effect of the antibacterial activity of Ag NPs on Escherichia coli and Staphylococcus aureus was tightly related to the reactive oxygen species accumulation. This research provides guidelines for the efficient green synthesis of Ag NPs and its antibacterial applications.     

Inorganic Nanotube/Organic Nanoparticle Hybrids for Enhanced Photoelectrochemical Properties

Inorganic/organic nanohybrids composed of arrayed TiO_2 nanotubes(Ti NTs)/porphyrin nanoparticles(NPs) have been fabricated via a wet chemical approach. The inorganic component, particularly the arrayed one-dimensional(1D) nanostructures, provides high charge-carrier mobility and rapid charge transport. The organic component exhibits extensive visible light absorption and good solution processability. Additionally, the geometric restraint by supramolecular assembly renders an improved photostability. A combination of these two components could thus allow for an efficient solar energy conversion. In this work, a colloid of porphyrin NPs prepared by a solvent exchange method is coated on anodic Ti NTs by means of a dip-coating treatment to form inorganic/organic hybrids. The hybrids exhibit an improvement on solar absorption and a significant enhancement on photocurrent generation at a small bias compared with individual component. Herein, the inorganic/organic nanohybrids are proved to be excellent photoanodes highly responsive to visible light and thus pave a way to discover new inorganic/organic assemblies for high-performance optoelectronic applications, as well as for device integration.     

Surface Tailoring of Nanoparticles via Mixed‐Charge Monolayers and Their Biomedical Applications

The recent convergence of nanomaterials and medicine has provided an expanding horizon for people to achieve encouraging advances in many biomedical applications such as cancer diagnosis and therapy. However, to realize desirable functions in the rather complex biological systems, a suitable surface coating is greatly in need for nanoparticles (NPs), regardless of the species. In this review, a recently developed surface modification strategy is highlighted—mixed‐charge monolayers—with an emphasis on the nanointerfaces of inorganic NPs. Two typical mixed‐charge gold NPs (AuNPs) prepared from surface modifications with different combinations of oppositely charged alkanethiols are shown as detailed examples to discuss how the mixed‐charge monolayer can help NPs meet the criteria for in vitro and in vivo biomedical applications, including those critical issues like colloidal stability, nonfouling properties, and smart responses (pH‐sensitivity) for tumor targeting.     

General synthesis of high-performing magneto-conjugated polymer core–shell nanoparticles for multifunctional theranostics

Recently,increasing attention has been paid to magneto-conjugated polymer core-shell nanopartides (NPs) as theranostic platforms.However,the utilization of surfactants and extra oxidizing agents with potential toxidty in synthesis,the lack of general methods for the controlled synthesis of various kinds of magnetic NP (MNP)@conjugated polymer NPs,and the difficulty of obtaining balanced magneto-optical properties have greatly limited the applications of magneto-conjugated polymers in theranostics.We developed an in situ surface polymerization method free of extra surfactants and oxidizing agents to synthesize MNP@polypyrrole (PPy) NPs with balanced,prominent magneto-optical properties.MNP@PPy NPs with an adjustable size,different shapes,and a controlled shell thickness were obtained using this method.The method was extended to synthesize other MNP-conjugated polymer core-shell NPs,such as MNP@polyaniline and MNP@poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS).We discuss the formation mechanism of the proposed method according to our experimental results.Finally,using the optical and magnetic properties of the obtained MNP@PEDOT:PSS NPs,in vivo multimodal imaging-guided hyperthermia was induced in mice,achieving an excellent tumor-ablation therapeutic effect.Our work is beneficial for extending the application of MNP-conjugated polymer core-shell NPs in the biomedical field.     

Interaction of colloidal nanoparticles with their local environment: the (ionic) nanoenvironment around nanoparticles is different from bulk and determines the physico-chemical properties of the nanoparticles

The physico-chemical properties of colloidal nanoparticles (NPs) are influenced by their local environment, as, in turn, the local environment influences the physico-chemical properties of the NPs. In other words, the local environment around NPs has a profound impact on the NPs, and it is different from bulk due to interaction with the NP surface. So far, this important effect has not been addressed in a comprehensive way in the literature. The vicinity of NPs can be sensitively influenced by local ions and ligands, with effects already occurring at extremely low concentrations. NPs in the Hückel regime are more sensitive to fluctuations in the ionic environment, because of a larger Debye length. The local ion concentration hereby affects the colloidal stability of the NPs, as it is different from bulk owing to Debye Hückel screening caused by the charge of the NPs. This can have subtle effects, now caused by the environment to the performance of the NP, such as for example a buffering effect caused by surface reaction on ultrapure ligand-free nanogold, a size quenching effect in the presence of specific ions and a significant impact on fluorophore-labelled NPs acting as ion sensors. Thus, the aim of this review is to clarify and give an unifying view of the complex interplay between the NP''s surface with their nanoenvironment.     

Bio-inspired supramolecular self-assembly towards soft nanomaterials

Supramolecular self-assembly has proven to be a reliable approach towards versatile nanomaterials based on multiple weak intermolecular forces. In this review, the development of bio-inspired supramolecular self-assembly into soft materials and their applications are summarized. Molecular systems used in bio-inspired “bottom-up self-assembly” involve small organic molecules, peptides or proteins, nucleic acids, and viruses. Self-assembled soft nanomaterials have been exploited in various applications such as inorganic nanomaterial synthesis, drug or gene delivery, tissue engineering, and so on.     

Review: nanoparticles and nanostructured materials in papermaking

The introduction of nanoparticles (NPs) and nanostructured materials (NSMs) in papermaking originally emerged from the perspective of improving processing operations and reducing material consumption. However, a very broad range of nanomaterials (NMs) can be incorporated into the paper structure and allows creating paper products with novel properties. This review is of interdisciplinary nature, addressing the emerging area of nanotechnology in papermaking focusing on resources, chemical synthesis and processing, colloidal properties, and deposition methods. An overview of different NMs used in papermaking together with their intrinsic properties and a link to possible applications is presented from a chemical point of view. After a brief introduction on NMs classification and papermaking, their role as additives or pigments in the paper structure is described. The different compositions and morphologies of NMs and NSMs are included, based on wood components, inorganic, organic, carbon-based, and composite NPs. In a first approach, nanopaper substrates are made from fibrillary NPs, including cellulose-based or carbon-based NMs. In a second approach, the NPs can be added to a regular wood pulp as nanofillers or used in coating compositions as nanopigments. The most important processing steps for NMs in papermaking are illustrated including the internal filling of fiber lumen, LbL deposition or fiber wall modification, with important advances in the field on the in situ deposition of NPs on the paper fibers. Usually, the manufacture of products with advanced functionality is associated with complex processes and hazardous materials. A key to success is in understanding how the NMs, cellulose matrix, functional additives, and processes all interact to provide the intended paper functionality while reducing materials waste and keeping the processes simple and energy efficient.     

Convenient synthesis and properties of polypropyleneimine dendrimer-functionalized polymer nanoparticles

A simple synthesis of polymer core-dendrimer shell nanoparticles (NPs) in the 15-20-nm-diameter range is presented. Amine-terminated polypropyleneimine (PPI) dendrimers DAB-dendri-(NH(2))(4) and DAB-dendri-(NH(2))(16) (DAB4 and DAB16) are covalently attached to the surface of primary polystyrene-based NPs bearing reactive chlorobenzyl groups produced by microemulsion polymerization in the presence of a cationic surfactant. The grafting readily proceeds under mild conditions and leads to translucent aqueous suspensions of core-shell-type NPs with a high density of peripheral amine groups that have been characterized relative to their size and chemical composition. The dendritic shell acts as a protective ionizable outer layer and provides an improvement of the colloidal stability in neutral and acidic media. The metal-binding capacity of the PPI dendrimers is retained, and spectrophotometric titrations show that the dendrimer-grafted NPs can trap a large number of Cu(2+) ions (more than 900 Cu per NP-DAB16). These properties make them potentially valuable templates for the elaboration of hybrid nanomaterials. The reactivity of the external amine groups is used to link covalently azobenzene chromophores (disperse Red 1 residues) through aza-Michael addition in aqueous suspension. This simple method gives access to colored NPs with high dye contents in the outer layer (up to 1000-1500 dye molecules per NP), which indicates that dendrimer-functionalized NPs are valuable building blocks for the construction of multifunctional nanomaterials.     

Thermoplasmonic‐Triggered Release of Loads from DNA‐Modified Hydrogel Microcapsules Functionalized with Au Nanoparticles or Au Nanorods

Microcapsules consisting of hydrogel shells cross‐linked by glucosamine–boronate ester complexes and duplex nucleic acids, loaded with dyes or drugs and functionalized with Au nanoparticles (Au NPs) or Au nanorods (Au NRs), are developed. Irradiation of Au NPs or Au NRs results in the thermoplasmonic heating of the microcapsules, and the dissociation of the nucleic acid cross‐linkers. The separation of duplex nucleic acid cross‐linkers leads to low‐stiffness hydrogel shells, allowing the release of loads. Switching off the light‐induced plasmonic heating results in the regeneration of stiff hydrogel shells protecting the microcapsules, leading to the blockage of release processes. The thermoplasmonic release of tetramethylrhodamine‐dextran, Texas Red‐dextran, doxorubicin‐dextran (DOX‐D), or camptothecin‐carboxymethylcellulose (CPT‐CMC) from the microcapsules is introduced. By loading the microcapsules with two different drugs (DOX‐D and CPT‐CMC), the light‐controlled dose release is demonstrated. Cellular experiments show efficient permeation of Au NPs/DOX‐D or Au NRs/DOX‐D microcapsules into MDA‐MB‐231 cancer cells and inefficient uptake by MCF‐10A epithelial breast cells. Cytotoxicity experiments reveal selective thermoplasmon‐induced cytotoxicity of the microcapsules toward MDA‐MB‐231 cancer cells as compared to MCF‐10A cells. Also, selective cytotoxicity towards MDA‐MB‐231 cancer cells upon irradiation of the Au NPs‐ and Au NRs‐functionalized microcapsules at λ = 532 or 910 nm is demonstrated.     

Multicolor FRET silica nanoparticles by single wavelength excitation

Fluorescent nanoparticles with multiple emission signatures by a single wavelength excitation are needed in multiplex bioanalysis and molecular imaging. We have prepared silica nanoparticles encapsulated with three organic dyes using a modified St?ber synthesis method. By varying the doping ratio of the three tandem dyes, fluorescence resonance energy transfer (FRET)-mediated emission signatures can be tuned to have the nanoparticles exhibit multiple colors under one single wavelength excitation. These nanoparticles are intensely fluorescent, highly photostable, uniform in size, and biocompatible. The acceptor emission of the FRET nanoparticles has generated a large Stokes shift, which implicates broad applications in biological labeling and imaging. Molecular recognition moieties, such as biotin, can be covalently attached to the nanoparticle surface to allow for specific binding to target molecules. These multicolor FRET silica nanoparticles can be used as barcoding tags for multiplexed signaling. By using these NPs, one can envision a dynamic, multicolor, colocalization methodology to follow proteins, nucleic acids, molecular machines, and assemblies within living systems.     

A general synthetic approach for obtaining cationic and anionic inorganic nanoparticles via encapsulation in amphiphilic copolymers

A series of amphiphilic copolymers with variable charge densities on their backbone is synthesized. Positively charged N,N,N-trimethylammonium-2-ethyl methacrylate iodide or negatively charged 2-(methacryloyloxy)ethylphosphonic acid and lauryl methacrylate are used as building blocks. When wrapped around hydrophobically capped inorganic nanoparticles (NPs), the latter are able to disperse in aqueous solutions. Using this method, positively as well as negatively charged colloidal NPs can be synthesized in a reliable way. The method presented herein allows the charge on the NPs to be adjusted to different negative and positive values by using polymers with a variable ratio of charged monomers and lauryl methacrylate. Virtually all kinds of hydrophobic inorganic NPs could be coated with these amphiphilic polymers. The coating procedure is demonstrated for Au particles as well as for CdSe/ZnS quantum dots. To date, wrapping amphiphilic polymers around NPs has led only to anionic NPs. The polymers synthesized in this work allow for positively charged NPs with a high colloidal stability.     

Eccentric Loading of Fluorogen with Aggregation‐Induced Emission in PLGA Matrix Increases Nanoparticle Fluorescence Quantum Yield for Targeted Cellular Imaging

A simple strategy is developed to prepare eccentrically or homogeneously loaded nanoparticles (NPs) using poly (DL‐lactide‐co‐glycolide) (PLGA) as the encapsulation matrix in the presence of different amounts of polyvinyl alcohol (PVA) as the emulsifier. Using 2,3‐bis(4‐(phenyl(4‐(1,2,2‐triphenylvinyl)‐phenyl)amino)‐phenyl)‐fumaronitrile (TPETPAFN), a fluorogen with aggregation‐induced emission (AIE) characteristics, as an example, the eccentrically loaded PLGA NPs show increased fluorescence quantum yields (QYs) as compared to the homogeneously loaded ones. Field emission transmission electron microscopy and fluorescence lifetime measurements reveal that the higher QY of the eccentrically loaded NPs is due to the more compact aggregation of AIE fluorogens that restricts intramolecular rotations of phenyl rings, which is able to more effectively block the non‐radiative decay pathways. The eccentrically loaded NPs show far red/near infrared emission with a high fluorescence QY of 34% in aqueous media. In addition, by using poly([lactide‐co‐glycolide]‐b‐folate [ethylene glycol]) (PLGA‐PEG‐folate) as the co‐encapsulation matrix, the obtained NPs are born with surface folic acid groups, which are successfully applied for targeted cellular imaging with good photostability and low cytotoxicity. Moreover, the developed strategy is also demonstrated for inorganic‐component eccentrically or homogeneously loaded PLGA NPs, which facilitates the synthesis of polymer NPs with controlled internal architectures.