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1.  Relaxation processes in hybrid organic-inorganic polymer nanosystems polymerized in situ 
Nanoscale Research Letters  2014;9(1):217.
The relaxation processes of hybrid organic-inorganic polymer nanosystems (OIS) synthesized by joint polymerization of organic and inorganic components were studied using methods of differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA), and broadband dielectric relaxation spectroscopy (DRS). The organic component was a mixture of two products: high-molecular-weight macrodiisocyanate (MDI) with low reactivity and low-molecular-weight isocyanate-containing modifier poly(isocyanate) (PIC) with high reactivity. Sodium silicate (SS) was used as inorganic component. The structures of the OIS obtained were in the form of hybrids with covalently connected building blocks and interpenetrating networks: weakly cross-linked network MDI/SS and highly cross-linked network PIC/SS. Depending on the MDI/PIC ratio, one of the networks was prevailing and created a continuous structure with domains of second network.
PACS
61.25.hk; 82.35.Lr; 64.70.pj
doi:10.1186/1556-276X-9-217
PMCID: PMC4019787  PMID: 24872804
Hybrid polymers; Organic-inorganic nanosystems; Joint polymerization; Interpenetrating networks; Relaxation phenomena
2.  Theranostic applications: Non-ionizing cellular and molecular imaging through innovative nanosystems for early diagnosis and therapy 
World Journal of Radiology  2011;3(10):249-255.
Modern medicine is expanding the possibilities of receiving “personalized” diagnosis and therapies, providing minimal invasiveness, technological solutions based on non-ionizing radiation, early detection of pathologies with the main objectives of being operator independent and with low cost to society. Our research activities aim to strongly contribute to these trends by improving the capabilities of current diagnostic imaging systems, which are of key importance in possibly providing both optimal diagnosis and therapies to patients. In medical diagnostics, cellular imaging aims to develop new methods and technologies for the detection of specific metabolic processes in living organisms, in order to accurately identify and discriminate normal from pathological tissues. In fact, most diseases have a “molecular basis” that detected through these new diagnostic methodologies can provide enormous benefits to medicine. Nowadays, this possibility is mainly related to the use of Positron Emission Tomography, with an exposure to ionizing radiation for patients and operators and with extremely high medical diagnostics costs. The future possible development of non-ionizing cellular imaging based on techniques such as Nuclear Magnetic Resonance or Ultrasound, would represent an important step towards modern and personalized therapies. During the last decade, the field of nanotechnology has made important progress and a wide range of organic and inorganic nanomaterials are now available with an incredible number of further combinations with other compounds for cellular targeting. The availability of these new advanced nanosystems allows new scenarios in diagnostic methodologies which are potentially capable of providing morphological and functional information together with metabolic and cellular indications.
doi:10.4329/wjr.v3.i10.49
PMCID: PMC3252558  PMID: 22229079
Intelligent nanosystems for cellular targeting; Magnetic resonance and ultrasound; Molecular imaging; Non-ionizing diagnostic techniques; Personalized medicine in the oncological and vascular field
3.  Nanomaterials for Cancer Therapy and Imaging 
Molecules and Cells  2011;31(4):295-302.
A variety of organic and inorganic nanomaterials with dimensions below several hundred nanometers are recently emerging as promising tools for cancer therapeutic and diagnostic applications due to their unique characteristics of passive tumor targeting. A wide range of nanomedicine platforms such as polymeric micelles, liposomes, dendrimers, and polymeric nanoparticles have been extensively explored for targeted delivery of anti-cancer agents, because they can accumulate in the solid tumor site via leaky tumor vascular structures, thereby selectively delivering therapeutic payloads into the desired tumor tissue. In recent years, nanoscale delivery vehicles for small interfering RNA (siRNA) have been also developed as effective therapeutic approaches to treat cancer. Furthermore, rationally designed multi-functional surface modification of these nanomaterials with cancer targeting moieties, protective polymers, and imaging agents can lead to fabrication versatile theragnostic nanosystems that allow simultaneous cancer therapy and diagnosis. This review highlights the current state and future prospects of diverse biomedical nanomaterials for cancer therapy and imaging.
doi:10.1007/s10059-011-0051-5
PMCID: PMC3933969  PMID: 21360197
cancer therapy; drug delivery system; imaging; nanoparticles; small interfering RNA
4.  In vivo and in vitro evaluation of octyl methoxycinnamate liposomes 
Solar radiation causes damage to human skin, and photoprotection is the main way to prevent these harmful effects. The development of sunscreen formulations containing nanosystems is of great interest in the pharmaceutical and cosmetic industries because of the many potential benefits. This study aimed to develop and evaluate an octyl methoxycinnamate (OMC) liposomal nanosystem (liposome/OMC) to obtain a sunscreen formulation with improved safety and efficacy by retaining OMC for longer on the stratum corneum.
Methods
The liposome/OMC nanostructure obtained was tested for enzymatic hydrolysis with lipase from Rhizomucor miehei and biodistribution with liposomes labeled with technetium-99m. The liposome/OMC formulation was then incorporated in a gel formulation and tested for ocular irritation using the hen’s egg test-chorio-allantoic membrane (HET-CAM) assay, in vitro and in vivo sun protection factor, in vitro release profile, skin biometrics, and in vivo tape stripping.
Results
The liposome/OMC nanosystem was not hydrolyzed from R. miehei by lipase. In the biodistribution assay, the liposome/OMC formulation labeled with technetium-99m had mainly deposited in the skin, while for OMC the main organ was the liver, showing that the liposome had higher affinity for the skin than OMC. The liposome/OMC formulation was classified as nonirritating in the HET-CAM test, indicating good histocompatibility. The formulation containing liposome/OMC had a higher in vivo solar photoprotection factor, but did not show increased water resistance. Inclusion in liposomes was able to slow down the release of OMC from the formulation, with a lower steady-state flux (3.9 ± 0.33 μg/cm2/hour) compared with the conventional formulation (6.3 ± 1.21 μg/cm2/hour). The stripping method showed increased uptake of OMC in the stratum corneum, giving an amount of 22.64 ± 7.55 μg/cm2 of OMC, which was higher than the amount found for the conventional formulation (14.57 ± 2.30 μg/cm2).
Conclusion
These results indicate that liposomes are superior carriers for OMC, and confer greater safety and efficacy to sunscreen formulations.
doi:10.2147/IJN.S51383
PMCID: PMC3864883  PMID: 24376350
sunscreen; liposome; tape stripping; technetium-99-m; lipase
5.  Rational Design and Synthesis of Freestanding Photoelectric Nanodevices as Highly Efficient Photocatalysts 
Nano letters  2010;10(5):1941-1949.
Photocatalysts are of significant interest for solar energy harvesting and conversion into chemical energy. However, the photocatalysts available to date are limited by either poor efficiency in the visible light range or insufficient photoelectrochemical stability. Here we report the rational design of a new generation of freestanding photoelectric nanodevices as highly efficient and stable photocatalysts by integrating a nanoscale photodiode with two redox catalysts in a single nanowire heterostructure. We show that a platinum-silicon-silver nanowire heterostructure can be synthesized to integrate a nanoscale metal-semiconductor Schottky diode encased in a protective insulating shell with two exposed metal catalysts. We further demonstrated that the Schottky diodes exhibited pronounced photovoltaic effect with nearly unity internal quantum efficiency, and that the integrated nanowire heterostructures could be used as highly efficient photocatalysts for a wide range of thermodynamically downhill and uphill reactions including photocatalytic degradation of organic dyes, reduction of metal ions and carbon dioxide using visible light. Our studies for the first time demonstrated the integration of multiple distinct functional components into a single nanostructure to form a standalone active nanosystem, and for the first time successfully realized a photoelectric nanodevice that is both highly efficient and highly stable throughout the entire solar spectrum. It thus opens a rational avenue to design and synthesize a new generation of photoelectric nanosystems with unprecedented efficiency and stability, and will impact broadly in areas including environmental remediation and solar fuel production.
doi:10.1021/nl101010m
PMCID: PMC2951842  PMID: 20373781
6.  Nanoparticle-based theranostic agents 
Advanced drug delivery reviews  2010;62(11):1064-1079.
Theranostic nanomedicine is emerging as a promising therapeutic paradigm. It takes advantage of the high capacity of nanoplatforms to ferry cargo and loads onto them both imaging and therapeutic functions. The resulting nanosystems, capable of diagnosis, drug delivery and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicine, and much research effort has been devoted toward that goal. A convenience in constructing such function-integrated agents is that many nanoplatforms are already, themselves, imaging agents. Their well developed surface chemistry makes it easy to load them with pharmaceutics and promote them to be theranostic nanosystems. Iron oxide nanoparticles, quantum dots, carbon nanotubes, gold nanoparticles and silica nanoparticles, have been previously well investigated in the imaging setting and are candidate nanoplatforms for building up nanoparticle-based theranostics. In the current article, we will outline the progress along this line, organized by the category of the core materials. We will focus on construction strategies and will discuss the challenges and opportunities associated with this emerging technology.
doi:10.1016/j.addr.2010.07.009
PMCID: PMC2988080  PMID: 20691229
Theranostics; drug delivery; gene delivery; nanomedicine; molecular imaging; iron oxide nanoparticles; quantum dots; gold nanoparticles; carbon nanotubes; silica nanoparticles
7.  Formulation and Evaluation of a Salted-out Isoniazid-loaded Nanosystem 
AAPS PharmSciTech  2008;9(1):174-181.
The purpose of this study was to develop a drug-loaded nanosystem that has the ability to achieve flexible yet rate-controlled release of model drug isoniazid (INH) employing either an aqueous or emulsion-based salting-out approach. Formulation conditions were aimed at reducing the polymeric size with subsequent rate-modulated INH release patterns from the polymeric nanosystem. The emulsion-based salted-out nanosystems had particle sizes ranging from 77–414 nm and a zeta potential of −24 mV. The dispersant dielectric constant was set at 78.5 and a conductivity of 3.99 mS/cm achieved. The reduced nanosystem size of the aqueous-based approach has demonstrated an intrinsically enhanced exposure of methacrylic acid-ethyl acrylate to zinc sulphate which was employed as a crosslinking reagent. This resulted in robustly interconnected polymeric supports in which INH was efficiently embedded and subsequently released. The multi-layer perceptron data obtained showed that the aqueous and emulsion-based salting out approaches had Power (law) (MSE = 0.020) and Linear (MSE = 0.038) relationships, respectively. Drug release from the nanosystems occurred in two phases with an initial burst-release in aqueous-based nanosystems (30–100%) and significantly lower bursts observed in emulsion-based nanosystems (20–65%) within the first 2 h. This was followed by a gradual exponential release phase over the remaining 12 h. The nanosystems developed demonstrated the ability to control the release of INH depending on the formulation approach adopted.
doi:10.1208/s12249-007-9016-6
PMCID: PMC2976898  PMID: 18446479
crosslinking; drug release; methacrylic acid-ethyl acrylate; nanoparticles; tuberculosis
8.  Preparation and evaluation of antimicrobial activity of nanosystems for the control of oral pathogens Streptococcus mutans and Candida albicans 
Background
Diseases that affect the buccal cavity are a public health concern nowadays. Chlorhexidine and nystatin are the most commonly used drugs for the control of buccal affections. In the search for more effective antimicrobials, nanotechnology can be successfully used to improve the physical chemical properties of drugs whilst avoiding the undesirable side effects associated with its use. Herein described are studies using nystatin and chlorhexidine with sodium montmorillonite (MMTNa), and chlorhexidine with β-cyclodextrin and two derivatives methyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin in the development of antimicrobial nanosystems.
Methods
The nanosystems were prepared by kneading and solubilization followed by freeze-drying technique. The nanosystems were characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). Nanosystem antimicrobial activity against Streptococcus mutans and Candida albicans strains was evaluated with inhibition halo analysis.
Results
The nanocarriers MMTNa and cyclodextrins showed good yields. XRPD, FTIR, and DSC analysis confirmed the proposed nanosystems formation and the suitability of the production methods. The nanosystems that showed best antimicrobial effect were chlorhexidine gluconate (CHX) and cyclodextrin inclusion complexes and CHX:MMTNa 60% cation exchange capacity – 24 hours.
Conclusion
The nanosystem formulations present higher stability for all chlorhexidine inclusion complexes compared with pure chlorhexidine. The nystatin nanosystems have the potential to mask the bitter taste, justifying subsequent in-vivo studies. For these reasons, further studies are being carried out to evaluate their application in professional formulations.
doi:10.2147/IJN.S25667
PMCID: PMC3218573  PMID: 22114490
sodium montmorillonite; chlorhexidine gluconate; buccal diseases; nanotechnology; cyclodextrins
9.  Non-Viral Delivery and Therapeutic Application of Small Interfering RNAs 
Acta Naturae  2013;5(3):35-53.
RNA interference (RNAi) is a powerful method used for gene expression regulation. The increasing knowledge about the molecular mechanism of this phenomenon creates new avenues for the application of the RNAi technology in the treatment of various human diseases. However, delivery of RNA interference mediators, small interfering RNAs (siRNAs), to target cells is a major hurdle. Effective and safe pharmacological use of siRNAs requires carriers that can deliver siRNA to its target site and the development of methods for protection of these fragile molecules from in vivo degradation. This review summarizes various strategies for siRNA delivery, including chemical modification and non-viral approaches, such as the polymer-based, peptide-based, lipid-based techniques, and inorganic nanosystems. The advantages, disadvantages, and prospects for the therapeutic application of these methods are also examined in this paper.
PMCID: PMC3848066  PMID: 24303201
small interfering RNA; RNA interference; non-viral delivery
10.  Hyaluronic acid based self-assembling nanosystems for CD44 target mediated siRNA delivery to solid tumors 
Biomaterials  2013;34(13):3489-3502.
Anticancer therapeutics employing RNA interference mechanism holds promising potentials for sequence-specific silencing of target genes. However targeted delivery of siRNAs to tumor tissues and cells and more importantly, their intracellular release at sites of interest still remains a major challenge that needs to be addressed before this technique could become a clinically viable option. In the current study, we have engineered and screened a series of CD44 targeting hyaluronic acid (HA) based self-assembling nanosystems for targeted siRNA delivery. The HA polymer was functionalized with lipids of varying carbon chain lengths/nitrogen content, as well as polyamines for assessing siRNA encapsulation. From the screens, several HA-derivatives were identified that could stably encapsulate/complex siRNAs and form self-assembled nanosystems, as determined by gel retardation assays and dynamic light scattering. Many HA derivatives could transfect siRNAs into cancer cells overexpressing CD44 receptors. Interestingly, blocking the CD44 receptors on the cells using free excess soluble HA prior to incubation of cy3-labeled-siRNA loaded HA nano-assemblies resulted in >90% inhibition of the receptor mediated uptake, confirming target specificity. In addition, SSB/PLK1 siRNA encapsulated in HA-PEI/PEG nanosystems demonstrated dose dependent and target specific gene knockdown in both sensitive and resistant A549 lung cancer cells overexpressing CD44 receptors. More importantly, these siRNA encapsulated nanosystems demonstrated tumor selective uptake and target specific gene knock down in vivo in solid tumors as well as in metastatic tumors. The HA based nanosystems thus portend to be promising siRNA delivery vectors for systemic targeting of CD44 overexpressing cancers including tumor initiating (stem-) cells and metastatic lesions.
doi:10.1016/j.biomaterials.2013.01.077
PMCID: PMC3636539  PMID: 23410679
Self-assembling nanosystems; siRNA delivery; Multidrug resistance; Tumor targeting; CD44; Hyaluronic acid
11.  Construction of a high-performance magnetic enzyme nanosystem for rapid tryptic digestion 
Scientific Reports  2014;4:6947.
A magnetic enzyme nanosystem have been designed and constructed by a polydopamine (PDA)-modification strategy. The magnetic enzyme nanosystem has well defined core-shell structure and a relatively high saturation magnetization (Ms) value of 48.3 emu g−1. The magnetic enzyme system can realize rapid, efficient and reusable tryptic digestion of proteins by taking advantage of its magnetic core and biofunctional shell. Various standard proteins (e.g. cytochrome C (Cyt-C), myoglobin (MYO) and bovine serum albumin (BSA)) have been used to evaluate the effectiveness of the magnetic enzyme nanosystem. The results show that the magnetic enzyme nanosystem can digest the proteins in 30 minutes, and the results are comparable to conventional 12 hours in-solution digestion. Furthermore, the magnetic enzyme nanosystem is also effective in the digestion of low-concentration proteins, even at as low as 5 ng μL−1 substrate concentration. Importantly, the system can be reused several times, and has excellent stability for storage. Therefore, this work will be highly beneficial for the rapid digestion and identification of proteins in future proteomics.
doi:10.1038/srep06947
PMCID: PMC4221791  PMID: 25374397
12.  Probing Nitrosyl Ligation of Surface-Confined Metalloporphyrins by Inelastic Electron Tunneling Spectroscopy 
ACS Nano  2013;7(6):5273-5281.
Complexes obtained by the ligation of nitric oxide (NO) to metalloporphyrins represent important model systems with biological relevance. Herein we report a molecular-level investigation of surface-confined cobalt tetraphenyl porphyrin (Co-TPP) species and their interaction with NO under ultrahigh vacuum conditions. It is demonstrated that individual NO adducts can be desorbed using the atomically sharp tip of a scanning tunneling microscope, whereby a writing process is implemented for fully saturated regular metalloporphyrin arrays. The low-energy vibrational characteristics of individual Co-TPP-nitrosyl complexes probed by inelastic electron tunneling spectroscopy (IETS) reveal a prominent signature at an energy of ≃31 meV. Using density functional theory-based IETS simulations—the first to be performed on such an extensive interfacial nanosystem—we succeed to reproduce the low-frequency spectrum for the NO-ligated complex and explain the absence of IETS activity for bare Co-TPP. Moreover, we can conclusively assign the IETS peak of NO-Co-TPP to a unique vibration mode involving the NO complexation site, namely, the in-plane Co–N–O rocking mode. In addition, we verify that the propensity rules previously designed on small aromatic systems and molecular fragments hold true for a metal–organic entity. This work notably permits one to envisage IETS spectroscopy as a sensitive tool to chemically characterize hybrid interfaces formed by complex metal–organic units and gaseous adducts.
doi:10.1021/nn4010582
PMCID: PMC3833350  PMID: 23718257
porphyrin; Ag(111); NO; STM; inelastic electron tunneling spectroscopy; DFT
13.  AFM, ESEM, TEM, and CLSM in liposomal characterization: a comparative study 
An outstanding aspect of pharmaceutical nanotechnology lies in the characterization of nanocarriers for targeting of drugs and other bioactive agents. The development of microscopic techniques has made the study of the surface and systems architecture more attractive. In the field of pharmaceutical nanosystems, researchers have collected vital information on size, stability, and bilayer organization through the microscopic characterization of liposomes. This paper aims to compare the results obtained by atomic force microscopy, environmental scanning electron microscopy, transmission electron microscopy, and confocal laser scanning microscopy to point out the limits and advantages of these applications in the evaluation of vesicular systems. Besides this comparative aim, our work proposes a simple confocal laser scanning microscopy procedure to rapidly and easily detect the liposomal membrane.
doi:10.2147/IJN.S14615
PMCID: PMC3065801  PMID: 21468358
atomic force microscopy; transmission electron microscopy; environmental scanning electron microscopy; confocal laser scanning microscopy
14.  Silver nanoparticles are broad-spectrum bactericidal and virucidal compounds 
The advance in nanotechnology has enabled us to utilize particles in the size of the nanoscale. This has created new therapeutic horizons, and in the case of silver, the currently available data only reveals the surface of the potential benefits and the wide range of applications. Interactions between viral biomolecules and silver nanoparticles suggest that the use of nanosystems may contribute importantly for the enhancement of current prevention of infection and antiviral therapies. Recently, it has been suggested that silver nanoparticles (AgNPs) bind with external membrane of lipid enveloped virus to prevent the infection. Nevertheless, the interaction of AgNPs with viruses is a largely unexplored field. AgNPs has been studied particularly on HIV where it was demonstrated the mechanism of antiviral action of the nanoparticles as well as the inhibition the transmission of HIV-1 infection in human cervix organ culture. This review discusses recent advances in the understanding of the biocidal mechanisms of action of silver Nanoparticles.
doi:10.1186/1477-3155-9-30
PMCID: PMC3199605  PMID: 21812950
Silver Nanoparticles; Virucides; Bactericides; HIV/AIDS; Antibacterial agents
15.  Biocompatible nanocomposite for PET/MRI hybrid imaging 
A novel nanocarrier system was designed and developed with key components uniquely structured at the nanoscale for early cancer diagnosis and treatment. In order to perform magnetic resonance imaging, hydrophilic superparamagnetic maghemite nanoparticles (NPs) were synthesized and coated with a lipophilic organic ligand. Next, they were entrapped into polymeric NPs made of biodegradable poly(lactic-co-glycolic acid) linked to polyethylene glycol. In addition, resulting NPs have been conjugated on their surface with a 2,2′-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid ligand for subsequent 68Ga incorporation. A cell-based cytotoxicity assay has been employed to verify the in vitro cell viability of human pancreatic cancer cells exposed to this nanosystem. Finally, in vivo positron emission tomography-computerized tomography biodistribution studies in healthy animals were performed.
doi:10.2147/IJN.S38107
PMCID: PMC3526150  PMID: 23271907
maghemite nanoparticles; organic coating; polymeric nanoparticles; magnetic resonance imaging; radiolabeling; positron emission tomography
16.  Nanowire systems: technology and design 
Nanosystems are large-scale integrated systems exploiting nanoelectronic devices. In this study, we consider double independent gate, vertically stacked nanowire field effect transistors (FETs) with gate-all-around structures and typical diameter of 20 nm. These devices, which we have successfully fabricated and evaluated, control the ambipolar behaviour of the nanostructure by selectively enabling one type of carriers. These transistors work as switches with electrically programmable polarity and thus realize an exclusive or operation. The intrinsic higher expressive power of these FETs, when compared with standard complementary metal oxide semiconductor technology, enables us to realize more efficient logic gates, which we organize as tiles to realize nanowire systems by regular arrays. This article surveys both the technology for double independent gate FETs as well as physical and logic design tools to realize digital systems with this fabrication technology.
doi:10.1098/rsta.2013.0102
PMCID: PMC3928901  PMID: 24567471
nanosystems; nanoelectronics; nanowire transistors; controllable polarity; regular arrays; logic synthesis
17.  Evaluation of Nanolipoprotein Particles (NLPs) as an In Vivo Delivery Platform 
PLoS ONE  2014;9(3):e93342.
Nanoparticles hold great promise for the delivery of therapeutics, yet limitations remain with regards to the use of these nanosystems for efficient long-lasting targeted delivery of therapeutics, including imparting functionality to the platform, in vivo stability, drug entrapment efficiency and toxicity. To begin to address these limitations, we evaluated the functionality, stability, cytotoxicity, toxicity, immunogenicity and in vivo biodistribution of nanolipoprotein particles (NLPs), which are mimetics of naturally occurring high-density lipoproteins (HDLs). We found that a wide range of molecules could be reliably conjugated to the NLP, including proteins, single-stranded DNA, and small molecules. The NLP was also found to be relatively stable in complex biological fluids and displayed no cytotoxicity in vitro at doses as high as 320 µg/ml. In addition, we observed that in vivo administration of the NLP daily for 14 consecutive days did not induce significant weight loss or result in lesions on excised organs. Furthermore, the NLPs did not display overt immunogenicity with respect to antibody generation. Finally, the biodistribution of the NLP in vivo was found to be highly dependent on the route of administration, where intranasal administration resulted in prolonged retention in the lung tissue. Although only a select number of NLP compositions were evaluated, the findings of this study suggest that the NLP platform holds promise for use as both a targeted and non-targeted in vivo delivery vehicle for a range of therapeutics.
doi:10.1371/journal.pone.0093342
PMCID: PMC3968139  PMID: 24675794
18.  Organic Nanofibers Embedding Stimuli-Responsive Threaded Molecular Components 
Journal of the American Chemical Society  2014;136(40):14245-14254.
While most of the studies on molecular machines have been performed in solution, interfacing these supramolecular systems with solid-state nanostructures and materials is very important in view of their utilization in sensing components working by chemical and photonic actuation. Host polymeric materials, and particularly polymer nanofibers, enable the manipulation of the functional molecules constituting molecular machines and provide a way to induce and control the supramolecular organization. Here, we present electrospun nanocomposites embedding a self-assembling rotaxane-type system that is responsive to both optical (UV–vis light) and chemical (acid/base) stimuli. The system includes a molecular axle comprised of a dibenzylammonium recognition site and two azobenzene end groups and a dibenzo[24]crown-8 molecular ring. The dethreading and rethreading of the molecular components in nanofibers induced by exposure to base and acid vapors, as well as the photoisomerization of the azobenzene end groups, occur in a similar manner to what observed in solution. Importantly, however, the nanoscale mechanical function following external chemical stimuli induces a measurable variation of the macroscopic mechanical properties of nanofibers aligned in arrays, whose Young’s modulus is significantly enhanced upon dethreading of the axles from the rings. These composite nanosystems show therefore great potential for application in chemical sensors, photonic actuators, and environmentally responsive materials.
doi:10.1021/ja5080322
PMCID: PMC4195382  PMID: 25264943
19.  Nanosystems for simultaneous imaging and drug delivery to T cells 
The AAPS Journal  2007;9(2):E171-E180.
The T-cell response defines the pathogenesis of many common chronic disease states, including diabetes, rheumatoid arthritis, and transplant rejection. Therefore, a diagnostic strategy that visualizes this response can potentially lead to early therapeutic intervention, avoiding catastrophic organ failure or prolonged sickness. In addition, the means to deliver a drug dose to those cells in situ with the same specificity used to image those cells would provide for a powerful therapeutic alternative for many disease states involving T cells. In this report, we review emerging nanosystems that can be used for simultaneous tracking and drug delivery to those cells. Because of their versatility, these systems—which combine specific receptor targeting with an imaging agent and drug delivery—are suited to both basic science and applications, from developing therapeutic strategies for autoimmune and alloimmune diseases, to noninvasive tracking of pathogenic T-cell migration.
doi:10.1208/aapsj0902019
PMCID: PMC2751406  PMID: 17614359
T cells; noninvasive imaging; drug delivery; nanoparticles
20.  Challenging the paradigm of nitrogen cycling: no evidence of in situ resource partitioning by coexisting plant species in grasslands of contrasting fertility 
Ecology and Evolution  2014;5(2):275-287.
In monoculture, certain plant species are able to preferentially utilize different nitrogen (N) forms, both inorganic and organic, including amino acids and peptides, thus forming fundamental niches based on the chemical form of N. Results from field studies, however, are inconsistent: Some showing that coexisting plant species predominantly utilize inorganic N, while others reveal distinct interspecies preferences for different N forms. As a result, the extent to which hypothetical niches are realized in nature remains unclear. Here, we used in situ stable isotope tracer techniques to test the idea, in temperate grassland, that niche partitioning of N based on chemical form is related to plant productivity and the relative availability of organic and inorganic N. We also tested in situ whether grassland plants vary in their ability to compete for, and utilize peptides, which have recently been shown to act as an N source for plants in strongly N-limited ecosystems. We hypothesized that plants would preferentially use NO3−-N and NH4+-N over dissolved organic N in high-productivity grassland where inorganic N availability is high. On the other hand, in low-productivity grasslands, where the availability of dissolved inorganic N is low, and soil availability of dissolved organic N is greater, we predicted that plants would preferentially use N from amino acids and peptides, prior to microbial mineralization. Turves from two well-characterized grasslands of contrasting productivity and soil N availability were injected, in situ, with mixtures of 15N-labeled inorganic N (NO3− and NH4+) and 13C15N labeled amino acid (l-alanine) and peptide (l-tri-alanine). In order to measure rapid assimilation of these N forms by soil microbes and plants, the uptake of these substrates was traced within 2.5 hours into the shoots of the most abundant plant species, as well as roots and the soil microbial biomass. We found that, contrary to our hypothesis, the majority of plant species across both grasslands took up most N in the form of NH4+, suggesting that inorganic N is their predominant N source. However, we did find that organic N was a source of N which could be utilized by plant species at both sites, and in the low-productivity grassland, plants were able to capture some tri-alanine-N directly. Although our findings did not support the hypothesis that differences in the availability of inorganic and organic N facilitate resource partitioning in grassland, they do support the emerging view that peptides represent a significant, but until now neglected, component of the terrestrial N cycle.
doi:10.1002/ece3.1244
PMCID: PMC4314261
Dissolved inorganic nitrogen; dissolved organic nitrogen; grassland productivity; nitrogen cycling; nitrogen partitioning; peptide; soil
21.  Organic selenium supplementation increased selenium concentrations in ewe and newborn lamb blood and in slaughter lamb meat compared to inorganic selenium supplementation 
Background
Selenium is part of the antioxidant defence system in animals and humans. The available selenium concentration in soil is low in many regions of the world. The purpose of this study was to evaluate the effect of organic versus inorganic selenium supplementation on selenium status of ewes, their lambs, and slaughter lambs.
Methods
Ewes on four organic farms were allocated five or six to 18 pens. The ewes were given either 20 mg/kg inorganic selenium as sodium selenite or organic selenium as selenized nonviable yeast supplementation for the two last months of pregnancy. Stipulated selenium concentrations in the rations were below 0.40 mg/kg dry matter. In addition 20 male lambs were given supplements from November until they were slaughtered in March. Silage, hay, concentrates, and individual ewe blood samples were taken before and after the mineral supplementation period, and blood samples were taken from the newborn lambs. Blood samples from ewes and lambs in the same pens were pooled. Muscle samples were taken from slaughter lambs in March. Selenium concentrations were determined by atomic absorption spectrometry with a hydride generator system. In the ANOVA model, selenium concentration was the continuous response variable, and selenium source and farm were the nominal effect variables. Two-sample t-test was used to compare selenium concentrations in muscle samples from the slaughtered lambs that received either organic or inorganic selenium supplements.
Results
In all ewe pens the whole blood selenium concentrations increased during the experimental period. In addition, ewe pens that received organic selenium had significantly higher whole blood selenium concentrations (mean 0.28 μg/g) than ewe pens that received inorganic selenium (mean 0.24 μg/g). Most prominent, however, was the difference in their lambs; whole blood mean selenium concentration in lambs from mothers that received organic selenium (mean 0.27 μg/g) was 30% higher than in lambs from mothers that received inorganic selenium (mean 0.21 μg/g). Slaughter lambs that received organic selenium had 50% higher meat selenium concentrations (mean 0.12 mg/kg wet weight) than lambs that received inorganic selenium (mean 0.08 mg/kg wet weight).
Conclusion
Organic selenium supplementation gave higher selenium concentration in ewe and newborn lamb blood and slaughter lamb meat than inorganic selenium supplementation.
doi:10.1186/1751-0147-50-7
PMCID: PMC2346462  PMID: 18377659
22.  Functionalized Nanosystems for Targeted Mitochondrial Delivery 
Mitochondrion  2011;12(2):190-201.
Mitochondrial dysfunction including oxidative stress and DNA mutations underlies the pathology of various diseases including Alzheimer’s disease and diabetes, necessitating the development of mitochondria targeted therapeutic agents. Nanotechnology offers unique tools and materials to target therapeutic agents to mitochondria. As discussed in this paper, a variety of functionalized nanosystems including polymeric and metallic nanoparticles as well as liposomes are more effective than plain drug and non-functionalized nanosystems in delivering therapeutic agents to mitochondria. Although the field is in its infancy, studies to date suggest the superior therapeutic activity of functionalized nanosystems for treating mitochondrial defects.
doi:10.1016/j.mito.2011.11.001
PMCID: PMC3299903  PMID: 22138492
Mitochondrial Targeted Delivery; Nanotechnology; Liposomes; Polymeric Nanoparticles; Metallic Nanoparticles
23.  Nanostructured systems containing babassu (Orbignya speciosa) oil as a potential alternative therapy for benign prostatic hyperplasia 
The oil of babassu tree nuts (Orbignya speciosa) is a potential alternative for treatment and prophylaxis of benign prostatic hyperplasia. Improved results can be obtained by drug vectorization to the hyperplastic tissue. The main objective of this work was the preparation and characterization of poly(lactic-co-glycolic acid) (PLGA) nanoparticle and clay nanosystems containing babassu oil (BBS). BBS was extracted from the kernels of babassu tree nuts and characterized by gas chromatography-mass spectrometry as well as 1H and 13C nuclear magnetic resonance. BBS-clay nanosystems were obtained by adding polyvinylpyrrolidone, Viscogel B8®, and BBS at a 2:1:1 mass ratio and characterized by X-ray diffraction, thermogravimetric analysis, infrared spectroscopy, and laser diffraction. The PLGA-BBS nanoparticles were prepared by the precipitation-solvent evaporation method. Mean diameter, polydispersity, zeta potential, and scanning electron microscopic images of the nanosystems were analyzed. Thermogravimetric analysis showed successful formation of the nanocomposite. PLGA nanoparticles containing BBS were obtained, with a suitable size that was confirmed by scanning electron microscopy. Both nanostructured systems showed active incorporation yields exceeding 90%. The two systems obtained represent a new and potentially efficient therapy for benign prostatic hyperplasia.
doi:10.2147/IJN.S47731
PMCID: PMC3753148  PMID: 23990721
babassu oil; nanocomposite; poly(lactic-co-glycolic acid); nanoparticles; benign prostatic hyperplasia; treatment; nanotechnology
24.  Overview of the role of nanotechnological innovations in the detection and treatment of solid tumors 
Nanotechnology, although still in its infantile stages, has the potential to revolutionize the diagnosis, treatment, and monitoring of disease progression and success of therapy for numerous diseases and conditions, not least of which is cancer. As it is a leading cause of mortality worldwide, early cancer detection, as well as safe and efficacious therapeutic intervention, will be indispensable in improving the prognosis related to cancers and overall survival rate, as well as health-related quality of life of patients diagnosed with cancer. The development of a relatively new field of nanomedicine, which combines various domains and technologies including nanotechnology, medicine, biology, pharmacology, mathematics, physics, and chemistry, has yielded different approaches to addressing these challenges. Of particular relevance in cancer, nanosystems have shown appreciable success in the realm of diagnosis and treatment. Characteristics attributable to these systems on account of the nanoscale size range allow for individualization of therapy, passive targeting, the attachment of targeting moieties for more specific targeting, minimally invasive procedures, and real-time imaging and monitoring of in vivo processes. Furthermore, incorporation into nanosystems may have the potential to reintroduce into clinical practice drugs that are no longer used because of various shortfalls, as well as aid in the registration of new, potent drugs with suboptimal pharmacokinetic profiles. Research into the development of nanosystems for cancer diagnosis and therapy is thus a rapidly emerging and viable field of study.
doi:10.2147/IJN.S50941
PMCID: PMC3904834  PMID: 24489467
nanosystems; targeted drug delivery; nanotheranostics; antineoplastic drugs; poor aqueous solubility; solid tumors
25.  Polysaccharide Nanosystems for Future Progress in Cardiovascular Pathologies 
Theranostics  2014;4(6):579-591.
Natural polysaccharides have received a lot of attention in the biomedical field. Indeed, sources of polysaccharides, extracted or produced from plants, bacteria, fungi or algae, are diverse and renewable. Moreover, recent progresses in polysaccharide chemistry and nanotechnologies allow elaborating new dedicated nanosystems. Polysaccharide-based nanosystems may be designed for interacting in several biological processes. In particular, the atherothrombotic pathology is highly concerned by polysaccharide-mediated recognition. Atherothrombotic diseases, regardless of the anatomical localization, remain the main causes of morbidity and mortality in the industrialized world. This review intends to provide an overview on polysaccharide-based nanosystems as drug delivery systems and targeted contrast agents for molecular imaging with an emphasis on the treatment and imaging of cardiovascular pathologies.
doi:10.7150/thno.7688
PMCID: PMC3982129  PMID: 24723980
Polysaccharides; Nanosystems; Atherothrombosis; Drug delivery; Molecular imaging.

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