Programmable Compartment Networks by Unraveling the Stress-Dependent Deformation of Polymer Vesicles.

Nanocontainers that can sense and respond to environmental stimuli like cells are desirable for next-generation delivery systems. However, it is still a grand challenge for synthetic nanocontainers to mimic or even surpass the shape adaption of cells, which may produce novel compartments for cargo loading. Here, this work reports the engineering of compartment network with a single polymer vesicle by unraveling osmotic stress-dependent deformation. Specifically, by manipulating the way in exerting the stress, sudden increase or gradual increase, polymer vesicles can either undergo deflation into the stomatocyte, a bowl-shaped vesicle enclosing a new compartment, or tubulation into the tubule of varied length. Such stress-dependent deformation inspired us to program the shape transformation of polymer vesicles, including tubulation, deflation, or first tubulation and then deflation. The coupled deformation successfully transforms the polymer vesicle into the stomatocyte with tubular arms and a network of two or three small stomatocytes connected by tubules. To the author's knowledge, these morphologies are still not accessed by synthetic nanocontainers. This work envisions that the network of stomatocytes may enable the loading of different catalysts to construct novel motile systems, and the well-defined morphology of vesicles helps to define the effect of morphology on cellar uptake.

Use of brome mosaic virus-like particles in feed, to deliver dsRNA targeting the white spot syndrome virus vp28 gene, reduces Penaeus vannamei mortality.

Numerous strategies have been investigated to combat viral infections in shrimp, specifically targeting the white spot syndrome virus (WSSV) that has caused outbreaks worldwide since the 1990s. One effective treatment involves intramuscular application of dsRNA-mediated interference against the viral capsid protein VP28. However, this approach presents challenges in terms of individual shrimp management, limiting its application on a large scale. To address this, our study aimed to evaluate the efficacy of oral delivery of protected dsRNA using chitosan nanoparticles or virus-like particles (VLPs) synthesized in brome mosaic virus (BMV). These delivery systems were administered before, during, and after WSSV infection to assess their therapeutic potential. Our findings indicate that BMV-derived VLPs demonstrated superior efficiency as nanocontainers for dsRNA delivery. Notably, the treatment involving vp28 dsRNA mixed in the feed and administered simultaneously to shrimp already infected with WSSV exhibited the highest survival rate (48%), while the infected group had a survival rate of zero, suggesting the potential efficacy of this prophylactic approach in commercial shrimp farms.

Adamantane-Terminated Polypeptides: Synthesis by N-Carboxyanhydride Polymerization and Template-Based Self-Assembly of Responsive Nanocontainers via Host-Guest Complexation with ß-Cyclodextrin.

The synthesis of adamantane-terminated polypeptides by N-carboxyanhydride (NCA) polymerization and their use in the template-based self-assembly of redox-responsive nanocontainers is described. Cyclodextrin vesicles (CDV) serve as a supramolecular template to anchor adamantane terminated polypeptides on to the surface of CDV and to form polypeptide shelled vesicles (PPSVss) which are stabilized by crosslinking with cystamin. Polypeptides are characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization (MALDI), and gel permeation chromatography, and nanocontainer formation at each step is confirmed by dynamic light scattering (DLS) and zeta potential measurements. MALDI confirms the presence of the adamantane at the end of the polymers, and isothermal titration calomatry (ITC) of the adamantane-terminated polypeptides with ß-cyclodextrin proves the capability of adamantane on the polypeptides to form host-guest inclusion complexes even with the longest polypeptides. Encapsulation of a model dye carboxyfluorescein in PPSVss and its redox-responsive release demonstrates the potential use of this novel type of completely biodegradable and biocompatible nanocontainer for the purpose of intracellullar delivery.

Production of Recombinant Protein Self-Assembly Nanocontainers in a Prokaryotic System.

We optimized a method for the preparation and purification of self-assembled protein nanocontainers EPN, the latest achievement in protein engineering. These nanocontainers are highly stable and provide the possibility of highly specific loading of a protein therapeutic drug. The described technique can be proposed as a tool for production of nanocontainers in a prokaryotic system. The obtained nanocontainers for the delivery of protein preparations can be used in the treatment of chronic, autoimmune, and oncological diseases.

Polymer Nanocontainers for Intracellular Delivery.

Carriers for intracellular delivery are required to overcome limitations of therapeutic agents such as low specificity, systemic toxicity, high clearance rate, and low therapeutic index. Nanocontainers comprised of an aqueous core and a polymer shell have received increasing attention because they readily combine stimuli response to improve intracellular payload release and surface modification to enhance selectivity towards the desired region of action. This Minireview summarizes the design and properties of polymer nanocontainers for intracellular delivery, classified according to the polymer architecture.

Nanocontainers for Analytical Applications.

Nanocontainers such as mesoporous silica particles and polymersomes are versatile structures containing holes or pores which are used for the entrapment of small molecules and the introduction of specific functionalities. They are widely applied in drug delivery, biomedicine, bioreactors, and analytical applications. In the last case, nanocontainers usually serve as amplification systems. They are hence synthesized to entrap signaling molecules and to bear functional moieties at the outer surface, which in turn enable specific analyte recognition and control of the nanocontainer pore permeability. This Review outlines the most important nanocontainer materials and discusses their synthesis, surface chemistry modifications, and strategies for molecule entrapment. Their advantages, challenges, and limitations are critically discussed in view of other common signal amplification strategies for different assay formats and various detection methods.

In vivo toxicity study of quatro stimuli nanocontainers in pregnant rats: Gestation, parturition and offspring evaluation.

The aim of the present study was to investigate the impact of intravenous administration of newly fabricated nanocontainers (NCs) on the last third of pregnancy in rats. Fifteen pregnant 3-month-old Wistar rats were separated into 3 groups. On the 15th and 17th day of pregnancy all animals received an intravenous administration of 1 ml of 15 mg of NCs (Group A), 1 ml of 5 mg NCs (Group B) while Control group received 1 ml of 0.9% NaCl. On the 14th and 17th of pregnancy ultrasonography was performed and the parameters evaluated were the width of placenta, the length and width of the embryonic sac, the foetus length and the heart rate. On parturition the number of pups per dam was evaluated. Half of the pups were euthanised the day after parturition and their liver and kidney was histologically evaluated and for the rest of the pups the body growth curve was evaluated until the age of 14 week. At the end of the 14th week the remaining pups were euthanised and their liver and kidney was histologically evaluated. At weaning the dams were euthanised and their liver and kidney was histologically evaluated. Ultrasonography: Baseline measurements of the width of placenta, the length and width of embryonic sac, the foetus length and the heart rate on the 14th day of pregnancy, revealed no statistical significant differences between groups. Comparison of the same values on the 17th day of pregnancy after 2 intravenous administrations of NCs showed no statistical significant effect on the respective parameters. The administration of NCs had no impact on the mean number of pups per dam. Additionally, no impact of the NCs on the body weights of the pups was observed on the 1st day after parturition. Moreover, comparisons between groups, for both sexes showed no difference on growth rate. During the histological evaluation no inflammatory, degenerative or neoplastic lesions were observed as far as the newborn, adult offspring and dams were concerned. According to our results no toxic impact of the low and high doses of the NCs was observed on the parameters selected to be evaluated.

Toward Artificial Mitochondrion: Mimicking Oxidative Phosphorylation in Polymer and Hybrid Membranes.

For energy supply to biomimetic constructs, a complex chemical energy-driven ATP-generating artificial system was built. The system was assembled with bottom-up detergent-mediated reconstitution of an ATP synthase and a terminal oxidase into two types of novel nanocontainers, built from either graft copolymer membranes or from hybrid graft copolymer/lipid membranes. The versatility and biocompatibility of the proposed nanocontainers was demonstrated through convenient system assembly and through high retained activity of both membrane-embedded enzymes. In the future, the nanocontainers might be used as a platform for the functional reconstitution of other complex membrane proteins and could considerably expedite the design of nanoreactors, biosensors, and artificial organelles.

Antimicrobial silver-filled silica nanorattles with low immunotoxicity in dendritic cells.

The progression in the use of orthopedic implants has led to an increase in the absolute number of implant infections, triggering a search for more effective antibacterial coatings. Nanorattles have recently gained interest in biomedical applications such as drug delivery, as encapsulation of the cargo inside the hollow structure provides a physical protection from the surrounding environment. Here, silver-containing silica nanorattles (Ag@SiO2) were evaluated for their antimicrobial potential and for their impact on cells of the immune system. We show that Ag@SiO2 nanorattles exhibited a clear antibacterial effect against Escherichia coli as well as Staphylococcus aureus found in post-operative infections. Immunotoxicological analyses showed that the particles were taken up through an active phagocytic process by dendritic cells of the immune system and did not affect their viability nor induce unwanted immunological effects. Silver-containing silica nanorattles thus fulfill several prerequisites for an antibacterial coating on surgical implants.

A Selection for Assembly Reveals That a Single Amino Acid Mutant of the Bacteriophage MS2 Coat Protein Forms a Smaller Virus-like Particle.

Virus-like particles are used to encapsulate drugs, imaging agents, enzymes, and other biologically active molecules in order to enhance their function. However, the size of most virus-like particles is inflexible, precluding the design of appropriately sized containers for different applications. Here, we describe a chromatographic selection for virus-like particle assembly. Using this selection, we identified a single amino acid substitution to the coat protein of bacteriophage MS2 that mediates a uniform switch in particle geometry from T = 3 to T = 1 icosahedral symmetry. The resulting smaller particle retains the ability to be disassembled and reassembled in vitro and to be chemically modified to load cargo into its interior cavity. The pair of 27 and 17 nm MS2 particles will allow direct examination of the effect of size on function in established applications of virus-like particles, including drug delivery and imaging.

Flexible Zirconium MOFs as Bromine-Nanocontainers for Bromination Reactions under Ambient Conditions.

A series of flexible MOFs (PCN-605, PCN-606, and PCN-700) are synthesized and applied to reversible bromine encapsulation and release. The chemical stability of these Zr-MOFs ensures the framework's integrity during the bromine adsorption, while the framework's flexibility allows for structural adaptation upon bromine uptake to afford stronger host-guest interactions and therefore higher bromine adsorption capacities. The flexible MOFs act as bromine-nanocontainers which elongate the storage time of volatile halides under ambient conditions. Furthermore, the bromine pre-adsorbed flexible MOFs can be used as generic bromine sources for bromination reactions giving improved yields and selectivities under ambient conditions when compared with liquid bromine.

Isoniazid@Fe2 O3 Nanocontainers and Their Antibacterial Effect on Tuberculosis Mycobacteria.

Isoniazid-filled Fe2 O3 hollow nanospheres (INH@Fe2 O3 , diameter <30 nm, 48 wt % INH-load) are prepared for the first time and suggested for tuberculosis therapy. After dextran-functionalization, the INH@Fe2 O3 @DEX nanocontainers show strong activity against Mycobacterium tuberculosis (M.tb.) and M.tb.-infected macrophages. The nanocontainers can be considered as "Trojan horses" and show efficient, active uptake into both M.tb.-infected macrophages and even into mycobacterial cells.

Controlling the size and morphology of supramolecular assemblies of viologen-resorcin[4]arene cavitands.

A novel class of self-assembling nanoparticles is formed with viologen-resorcin[4]arene cavitands; the association model is strongly controlled by their hydrophobicity. Interestingly, the cavitand assemblies are designed through click chemistry to form self-assembled noncovalently connected aggregates through counterion displacement. The iodide and benzoate ions are utilized as strongly polarizable counterions to induce cavitand self-assembly. The counterion-mediated decrease in hydrophilicity of the viologen-resorcin[4]arenes is the underlying trigger to induce particle formation. These particles can be used as nanocontainers and find their applications in delivery systems.

Free-standing alumina nanobottles and nanotubes pre-integrated into nanoporous alumina membranes.

A novel interfacial structure consisting of long (up to 5 µm), thin (about 300 nm), highly-ordered, free-standing, highly-reproducible aluminum oxide nanobottles and long tubular nanocapsules attached to a rigid, thin (less than 1 µm) nanoporous anodic alumina membrane is fabricated by simple, fast, catalyst-free, environmentally friendly voltage-pulse anodization. A growth mechanism is proposed based on the formation of straight channels in alumina membrane by anodization, followed by neck formation due to a sophisticated voltage control during the process. This process can be used for the fabrication of alumina nanocontainers with highly controllable geometrical size and volume, vitally important for various applications such as material and energy storage, targeted drug and diagnostic agent delivery, controlled drug and active agent release, gene and biomolecule reservoirs, micro-biologically protected platforms, nano-bioreactors, tissue engineering and hydrogen storage.

Cyclodextrin-modified zeolites: host-guest surface chemistry for the construction of multifunctional nanocontainers.

The functionalization of nanoporous zeolite L crystals with ß-cyclodextrin (CD) has been demonstrated. The zeolite surface was first modified with amino groups by using two different aminoalkoxysilanes. Then, 1,4-phenylene diisothiocyanate was reacted with the amino monolayer and used to bind CD heptamine by using its remaining isothiocyanate groups. The use of the different aminoalkoxysilanes, 3-aminopropyl dimethylethoxysilane (APDMES) and 3-aminopropyl triethoxysilane (APTES), led to drastic differences in uptake and release properties. Thionine was found to be absorbed and released from amino- and CD-functionalized zeolites when APDMES was used, whereas functionalization by APTES led to complete blockage of the zeolite channels. Fluorescence microscopy showed that the CD groups covalently attached to the zeolite crystals could bind adamantyl-modified dyes in a specific and reversible manner. This strategy allowed the specific immobilization of His-tagged proteins by using combined host-guest and His-tag-Ni-nitrilotriacetic acid (NTA) coordination chemistry. Such multifunctional systems have the potential for encapsulation of drug molecules inside the zeolite pores and non-covalent attachment of other (for example, targeting) ligand molecules on its surface.

Precise Localization and Simultaneous Bacterial Eradication of Biofilms Based on Nanocontainers with Successive Responsive Property toward pH and ATP.

The bacterial colonization of surfaces and subsequent biofilm formation are a great threat in medical therapy and clinical diagnosis. The complex internal structure and composition sets an enormous obstacle for the localization and removal of biofilms. In this study, we proposed a novel biofilm-targeted nanocontainer with successive responsive property toward pH and ATP for precise localization and simultaneous bacterial eradication, with an acidic and adenosine triphosphate (ATP)-rich microenvironment within biofilms, formed due to the accumulation of fatty acids and ATP in the three-dimensional enclosed structure, integrated as two successive indicators to improve the precision of biofilm identification and removal. The biofilm-targeted nanocontainer was composed of a ATP-responsive zeolitic imidazolate framework-90 (ZIF-90) core loaded with Rho 6G and doxorubicin hydrochloride (DOX) encapsulated in the pH-responsive amorphous calcium carbonate/poly(acrylic acid) (ACC/PAA) shell. In the presence of biofilms, the ACC/PAA shell and ZIF-90 core were successively degraded by the accumulated H+ and ATP within biofilms, resulting in the release of fluorescence indicators and antimicrobial agents. On the other hand, to meet the application requirements of different biofilm scenarios, the pH response ability of the nanocontainers could be adjusted by changing the metallic ions (Ni2+, Zn2+, and Cu2+) doped into the structure of the ACC/PAA shell. Owing to excellent water dispersion of the pH/ATP double-responsive ZIF-90@Zn-ACC/PAA nanocontainer, precise localization and simultaneous bacterial eradication was successfully realized via a simple spray process. The successive pH/ATP two-step unlocking processes endowed the nanocontainers high precision for localization and simultaneous eradication of biofilms, which made the proposed nanocontainers high promising in food safety and medical treatment.

TiO2 Nanocontainers Coconstructed Using Polymers and Corrosion Inhibitors for Anticorrosion Reinforcement of Waterborne Epoxy Coatings.

Stimulus-responsive coatings can provide active corrosion protection in response to environmental changes, but they have not reached their anticipated application prospects because of the intricate preparation processes of hollow materials and methods for loading corrosion inhibitors. Herein, polyaniline molybdate corrosion inhibitor and polydopamine-wrapped titanium dioxide nanocontainers (named TiO2/PANI-MoO42-/PDA) are synthesized via a simple three-step electrostatic assembly technique. Introducing TiO2/PANI-MoO42-/PDA nanocontainers in smart waterborne epoxy (WEP) coatings affords the latter with high barriers and long-term corrosion protection. The successful deposition of each layer on the TiO2 nanocontainer surface was validated via Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and X-ray photoelectron spectroscopy. Release test results show that the molybdate corrosion inhibitor exhibits notable pH-responsive activity under acidic conditions and slow release in neutral environments, which improves the corrosion resistance of coatings. The addition of synthetic nanocontainers greatly improves the impermeability of WEP coatings. The charge transfer resistance of WEP/TiO2/PANI-MoO42-/PDA coatings is 1.79 × 1011 Ω cm2 after 30 day immersion in a 3.5 wt % NaCl solution, which is 3.32 × 105 times higher than that of WEP coatings. WEP/TiO2/PANI-MoO42-/PDA coatings remain uniform and reliable, even after 50 days of salt spray exposure. The excellent corrosion protection of WEP/TiO2/PANI-MoO42-/PDA coatings is attributed to (1) the enhanced dispersion and compatibility of PDA in the coating for nanocontainers, (2) the combination of phenolic hydroxyl groups of PDA and Fe, which inhibit corrosion activity on the exposed metal surface, and (3) the on-demand release of the MoO42- inhibitor, which provides sustained passivation protection. This work proposes a strategy to simplify the preparation of responsive long-term anticorrosion coatings and extend their service lives.

Artificial Protein Cages Assembled via Gold Coordination.

Artificial protein cages made from multiple copies of a single protein can be produced such that they only assemble upon addition of a metal ion. Consequently, the ability to remove the metal ion triggers protein-cage disassembly. Controlling assembly and disassembly has many potential uses including cargo loading/unloading and hence drug delivery. TRAP-cage is an example of such a protein cage which assembles due to linear coordination bond formation with Au(I) which acts to bridge constituent proteins. Here we describe the method for production and purification of TRAP-cage.

ORMOSIL Coatings Enriched with CeO2 (5-ATDT)-Ceramic Nanocontainers for Enhanced Protection of HDG Steel Used in Concrete.

This paper reports developing an innovative method of anticorrosion protection based on organically modified silica (ORMOSIL) enriched with CeO2 ceramic nanocontainers loaded with 5-amino-1, 3, 4-thiadiazole-2-thiol (5-ATDT) on hot-dip galvanized zinc (HDG) steel used to strengthen cement in concrete. The chemistry of ORMOSIL coatings and the production of CeO2 ceramic nanocontainers are described in detail for reproduction by other researchers. The anticorrosion properties of these novel coatings were investigated through frequency response analysis (FRA). As a result, the coatings HDG-ORMOSIL + CeO2 (5-ATDT) were better than the samples of HDG steel, HDG-ORMOSIL, and HDG-ORMOSIL + CeO2 (EMPTY) by a factor of 1033.60, 109.21, and 7.76 in terms of anticorrosion protection, respectively.

Synthesis and Electrochemical Evaluation of MSNs-PbAE Nanocontainers for the Controlled Release of Caffeine as a Corrosion Inhibitor.

In this paper, a controlled-release system of caffeine as a corrosion inhibitor was obtained by encapsulating it in MCM-41 silica nanoparticles coated with a poly(ß-amino ester) (PbAE), a pH-sensible polymer. Encapsulation was verified using Fourier transform infrared spectroscopy (FTIR) and thermogravimetry (TGA). The release of caffeine from the nanocontainers was analyzed in electrolytes with pH values of 4, 5, and 7 using UV-Vis, showing a 21% higher release in acidic electrolytes than in neutral electrolytes, corroborating its pH sensitivity. Electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization were used to determine the inhibition mode and efficiency of the encapsulated and free caffeine. The caffeine released from the nanocontainers showed the highest efficiency, which was 85.19%. These results indicate that these nanocontainers could have potential use in smart anticorrosion coating applications.