Targeted Drug Delivery in Covalent Organic Nanosheets (CONs) via Sequential Postsynthetic Modification.

Covalent organic nanosheets (CONs) have emerged as a new class of functional two-dimensional (2D) porous organic polymeric materials with a high accessible surface, diverse functionality, and chemical stability. They could become versatile candidates for targeted drug delivery. Despite their many advantages, there are limitations to their use for target specific drug delivery. We anticipated that these drawbacks could be overturned by judicious postsynthetic modification steps to use CONs for targeted drug delivery. The postsynthetic modification would not only produce the desired functionality, it would also help to exfoliate to CONs as well. In order to meet this requirement, we have developed a facile, salt-mediated synthesis of covalent organic frameworks (COFs) in the presence of p-toluenesulfonic acid (PTSA). The COFs were subjected to sequential postsynthetic modifications to yield functionalized targeted CONs for targeted delivery of 5-fluorouracil to breast cancer cells. This postsynthetic modification resulted in simultaneous chemical delamination and functionalization to targeted CONs. Targeted CONs showed sustained release of the drug to the cancer cells through receptor-mediated endocytosis, which led to cancer cell death via apoptosis. Considering the easy and facile COF synthesis, functionality based postsynthetic modifications, and chemical delamination to CONs for potential advantageous targeted drug delivery, this process can have a significant impact in biomedical applications.

Selective Molecular Sieving in Self-Standing Porous Covalent-Organic-Framework Membranes.

Self-standing, flexible, continuous, and crack-free covalent-organic-framework membranes (COMs) are fabricated via a simple, scalable, and highly cost-effective methodology. The COMs show long-term durability, recyclability, and retain their structural integrity in water, organic solvents, and mineral acids. COMs are successfully used in challenging separation applications and recovery of valuable active pharmaceutical ingredients from organic solvents.

Chemically Delaminated Free-Standing Ultrathin Covalent Organic Nanosheets.

Covalent organic nanosheets (CONs) are a new class of porous thin two-dimensional (2D) nanostructures that can be easily designed and functionalized and could be useful for separation applications. Poor dispersion, layer restacking, and difficult postsynthetic modifications are the major hurdles that need to be overcome to fabricate scalable CON thin films. Herein, we present a unique approach for the chemical exfoliation of an anthracene-based covalent organic framework (COF) to N-hexylmaleimide-functionalized CONs, to yield centimeter-sized free-standing thin films through layer-by-layer CON assembly at the air-water interface. The thin-layer fabrication technique presented here is simple, scalable, and does not require any surfactants or stabilizing agents.

Self-Exfoliated Guanidinium-Based Ionic Covalent Organic Nanosheets (iCONs).

Covalent organic nanosheets (CONs) have emerged as functional two-dimensional materials for versatile applications. Although π-π stacking between layers, hydrolytic instability, possible restacking prevents their exfoliation on to few thin layered CONs from crystalline porous polymers. We anticipated rational designing of a structure by intrinsic ionic linker could be the solution to produce self-exfoliated CONs without external stimuli. In an attempt to address this issue, we have synthesized three self-exfoliated guanidinium halide based ionic covalent organic nanosheets (iCONs) with antimicrobial property. Self-exfoliation phenomenon has been supported by molecular dynamics (MD) simulation as well. Intrinsic ionic guanidinium unit plays the pivotal role for both self-exfoliation and antibacterial property against both Gram-positive and Gram-negative bacteria. Using such iCONs, we have devised a mixed matrix membrane which could be useful for antimicrobial coatings with plausible medical benefits.

Gadolinium(III)-Based Porous Luminescent Metal-Organic Frameworks for Bimodal Imaging.

GdIII -based metal-organic frameworks, Gd-pDBI-1 and Gd-pDBI-2, have been synthesized using the linker pDBI (pDBI=1,4-bis(5-carboxy-1H-benzimidazole-2yl)benzene). They exhibited structural diversity due to subtle change in reaction constituents. Owing to the judicious choice of the fluorescent linker, the materials could be used for bimodal imaging (fluorescent and magnetic resonance) and displayed a modest T1 relaxivity value.

Simple synthesis of biocompatible biotinylated porous hexagonal ZnO nanodisc for targeted doxorubicin delivery against breast cancer cell: In vitro and in vivo cytotoxic potential.

Targeted drug delivery with porous materials features great promise as improved therapeutic potential for treatment of various diseases. In the present study we have attempted a microwave synthesis of porous hexagonal nanodisc of zinc oxide (PZHD) for the first time and its subsequent targeted delivery to breast cancer cells, MCF7. PZHD has been fabricated suitably with 3-aminopropyltriethoxysilane to impart additional stability and surface amines to anchor site directing ligand NHS-biotin. Biotinylated scaffold showed targeted delivery of anticancer drug doxorubicin and pH triggered release to MCF 7 cells with preferential distribution on specified domain. A detailed in vitro cytotoxicity study was associated with it to evaluate the mode of action of Dox loaded PZHD on MCF-7 cells by means of cell cycle analysis, apoptosis assays, Western blot and immuno-fluorescence image analysis. The efficacy of the Dox loaded PZHD was further validated from our in vivo tumor regression studies. Finally, the whole study has been supported by in vitro and in vivo bio-safety studies which also signified its biocompatibility with real time applications. To the best of our knowledge this is the first effort to use biotinylated PZHD for targeted delivery of doxorubicin within MCF 7 cells with a detailed study of its mechanistic application. This study might thus hold future prospects for therapeutic intervention for treatment of cancer.

Copper nanoparticle (CuNP) nanochain arrays with a reduced toxicity response: a biophysical and biochemical outlook on Vigna radiata.

Copper deficiency or toxicity in agricultural soil circumscribes a plant's growth and physiology, hampering photochemical and biochemical networks within the system. So far, copper sulfate (CS) has been used widely despite its toxic effect. To get around this long-standing problem, copper nanoparticles (CuNPs) have been synthesized, characterized, and tested on mung bean plants along with commercially available salt CS, to observe morphological abnormalities enforced if any. CuNPs enhanced photosynthetic activity by modulating fluorescence emission, photophosphorylation, electron transport chain (ETC), and carbon assimilatory pathway under controlled laboratory conditions, as revealed from biochemical and biophysical studies on treated isolated mung bean chloroplast. CuNPs at the recommended dose worked better than CS in plants in terms of basic morphology, pigment contents, and antioxidative activities. CuNPs showed elevated nitrogen assimilation compared to CS. At higher doses CS was found to be toxic to the plant system, whereas CuNP did not impart any toxicity to the system including morphological and/or physiological alterations. This newly synthesized polymer-encapsulated CuNPs can be utilized as nutritional amendment to balance the nutritional disparity enforced by copper imbalance.

Microwave synthesis of ZnO@mSiO2 for detailed antifungal mode of action study: understanding the insights into oxidative stress.

A simple chemical method has been devised for deliberate incorporation of zinc oxide nanoparticles (ZNPs) within mesoporous nanosilica (mSiO2) matrix to yield zinc oxide nanoparticles embedded in mesoporous nanosilica (ZnO@mSiO2). ZnO@mSiO2 inhibited the growth of four strains of fungi in a dose dependant manner. A series of biochemical assays revealed generation of oxidative stress from ZnO@mSiO2 for such biocidal response. We proposed transient superoxide and its subsequent conversion to H2O2 played a pivotal role behind such biocidal response as revealed from our systematic evaluation. This resulted morphological alteration of fungi through increase in number of facets, in correlation we found up-regulation in oxidative stress related genes. Bioavailability within the fungal sample was confirmed from microscopic, spectroscopic, biophysical techniques. Protein carbonylation of fungal species was the chemical outcome of such above mentioned stress and quantified by high performance liquid chromatography (HPLC) via subsequent hydrazone derivatization. Several in vitro and in vivo evaluations revealed the biocompatibility of ZnO@mSiO2. Altogether this report claims a new biocidal agent with a detailed mode of action focusing on the origin and quantification of oxidative stress through biophysical and biochemical techniques for the first time for real time applications.

Manganese nanoparticles: impact on non-nodulated plant as a potent enhancer in nitrogen metabolism and toxicity study both in vivo and in vitro.

Mung bean plants were grown under controlled conditions and supplemented with macro- and micronutrients. The objective of this study was to determine the response of manganese nanoparticles (MnNP) in nitrate uptake, assimilation, and metabolism compared with the commercially used manganese salt, manganese sulfate (MS). MnNP was modulated to affect the assimilatory process by enhancing the net flux of nitrogen assimilation through NR-NiR and GS-GOGAT pathways. This study was associated with toxicological investigation on in vitro and in vivo systems to promote MnNP as nanofertilizer and can be used as an alternative to MS. MnNP did not impart any toxicity to the mice brain mitochondria except in the partial inhibition of complex II-III activity in ETC. Therefore, mitochondrial dysfunction and neurotoxicity, which were noted by excess usage of elemental manganese, were prevented. This is the first attempt to highlight the nitrogen uptake, assimilation, and metabolism in a plant system using a nanoparticle to promote a biosafe nanomicronutrient-based crop management.

Mechanical downsizing of a gadolinium(III)-based metal-organic framework for anticancer drug delivery.

A Gd(III) -based porous metal-organic framework (MOF), Gd-pDBI, has been synthesized using fluorescent linker pDBI (pDBI=(1,4-bis(5-carboxy-1H-benzimidazole-2-yl)benzene)), resulting in a three-dimensional interpenetrated structure with a one-dimensional open channel (1.9×1.2 nm) filled with hydrogen-bonded water assemblies. Gd-pDBI exhibits high thermal stability, porosity, excellent water stability, along with organic-solvent and mild acid and base stability with retention of crystallinity. Gd-pDBI was transformed to the nanoscale regime (ca. 140 nm) by mechanical grinding to yield MG-Gd-pDBI with excellent water dispersibility (>90 min), maintaining its porosity and crystallinity. In vitro and in vivo studies on MG-Gd-pDBI revealed its low blood toxicity and highest drug loading (12 wt %) of anticancer drug doxorubicin in MOFs reported to date with pH-responsive cancer-cell-specific drug release.

High throughput electron transfer from carbon dots to chloroplast: a rationale of enhanced photosynthesis.

A biocompatible amine functionalized fluorescent carbon dots were developed and isolated for gram scale applications. Such carbogenic quantum dots can strongly conjugate over the surface of the chloroplast and due to that strong interaction the former can easily transfer electrons towards the latter by assistance of absorbed light or photons. An exceptionally high electron transfer from carbon dots to the chloroplast can directly effect the whole chain electron transfer pathway in a light reaction of photosynthesis, where electron carriers play an important role in modulating the system. As a result, carbon dots can promote photosynthesis by modulating the electron transfer process as they are capable of fastening the conversion of light energy to the electrical energy and finally to the chemical energy as assimilatory power (ATP and NADPH).

Photochemical modulation of biosafe manganese nanoparticles on Vigna radiata: a detailed molecular, biochemical, and biophysical study.

Manganese (Mn) is an essential element for plants which intervenes mainly in photosynthesis. In this study we establish that manganese nanoparticles (MnNP) work as a better micronutrient than commercially available manganese salt, MnSO4 (MS) at recommended doses on leguminous plant mung bean (Vigna radiata) under laboratory condition. At higher doses it does not impart toxicity to the plant unlike MS. MnNP-treated chloroplasts show greater photophosphorylation, oxygen evolution with respect to control and MS-treated chloroplasts as determined by biophysical and biochemical techniques. Water splitting by an oxygen evolving complex is enhanced by MnNP in isolated chloroplast as confirmed by polarographic and spectroscopic techniques. Enhanced activity of the CP43 protein of a photosystem II (PS II) Mn4Ca complex influenced better phosphorylation in the electron transport chain in the case of MnNP-treated chloroplast, which is evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and corresponding Western blot analysis. To the best of our knowledge this is the first report to augment photosynthesis using MnNP and its detailed correlation with different molecular, biochemical and biophysical parameters of photosynthetic pathways. At effective dosage, MnNP is found to be biosafe both in plant and animal model systems. Therefore MnNP would be a novel potential nanomodulator of photochemistry in the agricultural sector.

Luminescent S-doped carbon dots: an emergent architecture for multimodal applications.

A facile route has been developed to synthesise and isolate sulphur doped fluorescent carbon dots for the first time. Such carbogenic quantum dots exhibit a wide band gap of 4.43 eV with a high open circuit voltage (VOC) of 617 mV along with a fill factor (FF) as high as 37%, using phenyl-C60-butyric acid methyl ester (PCBM) as the electron transporting layer. Besides the wide band gap, which is useful in the fabrication of solar cells, sulphur modified carbon dots also exhibit a high fluorescence quantum yield of 11.8% without any additional surface passivation, producing a unique fluorescent probe for further applications. In addition, the particles have a strong tendency to interact with the surface of gold nanoparticles and produce a thin fluorescent layer over their surfaces. Moreover, as they are completely biocompatible in nature, the highly fluorescent S-doped carbon dots have a strong potential for use in bioimaging applications. Interestingly, owing to the presence of oxygen and sulphur functionality, the highly negatively charged particles can easily bind with positively charged DNA-PEI complexes, simply by mixing them, and after interaction with DNA, bright blue fluorescence has been observed under an excitation wavelength of 405 nm .

Biochemical-, biophysical-, and microarray-based antifungal evaluation of the buffer-mediated synthesized nano zinc oxide: an in vivo and in vitro toxicity study.

Here we describe a simple, novel method of zinc oxide nanoparticle (ZNP) synthesis and physicochemical characterization. The dose-dependent antifungal effect of ZNPs, compared to that of micronized zinc oxide (MZnO), was studied on two pathogenic fungi: Aspergillus niger and Fusarium oxysporum. Superoxide dismutase (SOD) activity, ascorbate peroxidase activity, catalase activity, glutathione reductase (GR) activity, thiol content, lipid peroxidation, and proline content in ZNP-treated fungal samples were found to be elevated in comparison to the control, which strongly suggested that the antifungal effect of ZNPs was due to the generation of reactive oxygen species (ROS). Protein carbonylation, another marker of oxidative stress, was also evaluated by the dinitrophenyl hydrazine (DNPH) binding assay and Fourier transform infrared (FTIR) spectral analysis followed by Western blot and microarray analysis of fungal samples to confirm ROS generation by ZNPs. Micrographic studies for the morphological analysis of fungal samples (ZNP-treated and a control) exhibited an alteration in fungal morphology. The bioavailability of ZNPs on fungal cell was confirmed by energy-dispersive X-ray (EDX) analysis followed by high-resolution transmission electron microscopy (HR-TEM) and confocal microscopic analysis of the fungal samples. In vivo acute oral toxicity, acetylcholine esterase activity, and a fertility study using a mice model were also investigated for ZNPs. The long-term toxicity of ZNPs through intravenous injection was evaluated and compared to that of MZnO. The in vitro comparative toxicity of ZNPs and MZnO was evaluated on MRC-5 cells with the help of water-soluble tetrazolium (WST-1) and lactate dehydrogenase (LDH) assays. These results suggested that ZNPs could be used as an effective fungicide in modern medical and agricultural sciences.

Comparative analysis of stability and toxicity profile of three differently capped gold nanoparticles for biomedical usage.

Nowadays gold nanoparticle (GNP) is increasingly being used in drug delivery and diagnostics. Here we have reported a comparative analysis of detailed stability and toxicity (in vitro and in vivo) profile of three water soluble spherical GNPs, having nearly similar size, but the surfaces of which were modified with three different capping materials aspartic acid (GNPA), trisodium citrate dihydrate (GNPC) or bovine serum albumin (GNPB). Spectral analyses on the stability of these GNPs revealed that depending on the nature of capping agents, GNPs behave differently at different environmental modalities like wide range of pH, high salt concentrations, or in solutions and buffers of biological usage. GNPB was found to be extremely stable, where capped protein molecule successfully maintained its secondary structure and helicity on the nanoparticle, whereas colloidal stability of GNPA was most susceptible to altered conditions. In vitro cytotoxicity of these nanoparticle formulations in vitro were determined by water soluble tetrazolium and lactate dehydrogenase assay in human fibroblast cell line (MRC-5) and acute oral toxicity was performed in murine model system. All the GNPs were non-toxic to MRC-5 cells. GNPC had slight hepatotoxic and nephrotoxic responses. Hepatotoxicity was also evident for GNPA treatment. Present study established that there is a correlation between capping material and stability together with toxicity of nanoparticles. GNPB was found to be most biocompatible among the three GNPs tested.

Fabrication of multi-structure nanocarbons from carbon xerogel: a unique scaffold towards bio-imaging.

A novel route has been developed to fabricate different carbon nanostructures having individual morphology of carbon nanoparticles: nanofullerene, nanocube, nanoleaf and porous nanorods, through the combustion of carbon xerogel with nitric acid. These fabricated nanostructures exhibited bright green fluorescence under the exposure of UV light.