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The elevated glutathione (GSH) level in cancer cells contributes to the poor response to chemotherapy and necessitates the use of maximum tolerated drug doses, leading to myriad side effects. We have developed a biocompatible and fluorescently trackable nanosystem, iron(III)-bound nanocarbonaceous polyphenol (FeNCP), to modulate the available GSH pool in cancer cells for synergistic effects in treatments with a cytotoxic anticancer drug, doxorubicin (Dox). This nanosystem was designed using a nanoscale carbon system as a platform to generate a GSH-responsive gallic acid-iron complex. The effective interaction between FeNCP and GSH was probed in PBS (pH 7.4) and cell lysates using UV-Vis, fluorescence spectrophotometry

Heart failure or myocardial infarction (MI) is one of the world's leading causes of death. Post MI, the heart can develop pathological conditions such as ischemia, inflammation, fibrosis, and left ventricular dysfunction. However, current surgical approaches are sufficient for enhancing myocardial perfusion but are unable to reverse the pathological changes. Tissue engineering and regenerative medicine approaches have shown promising effects in the repair and replacement of injured cardiomyocytes. Additionally, biomaterial scaffolds with or without stem cells are established to provide an effective environment for cardiac regeneration. Excipients loaded with growth factors, cytokines, oligonucleotides, and exosomes are found to help in such cardiac eventualities by promoting angiogenesis, cardiomyocyte proliferation, and reducing fibrosis, inflammation, and apoptosis. Injectable hydrogels, nanocarriers, cardiac patches, and vascular grafts are some excipients that can help the self-renewal in the damaged heart but are not understood well yet, in the context of used biomaterials. This review focuses on the use of various biomaterial-based approaches for the regeneration and repair of cardiac tissue postoccurrence of MI. It also discusses the outlines of cardiac remodeling and current therapeutic approaches after myocardial infarction, which are translationally important with respect to used biomaterials. It provides comprehensive details of the biomaterial-based regenerative approaches, which are currently the focus of the research for cardiac repair and regeneration and can provide a broad outline for further improvements.

Figure S1. Protocol of CD44 peptide conjugation on NIC-Veh nanoparticles; Figure S2. Physico-chemical properties of NIC-Veh; Figure S3. Bright field images of breast cancer cells (A-C) MDA-MB231 and (D-F) MCF-7 cells without treatment (A, B) or with treatment of (B, E) niclosamide and (C, F) CD44-NIC-Veh for 48h at 20 μM of niclosamide concentration; Figure S4. Flow assisted cell scanning histograms and cell growth analysis post treatment in MCF-7 and MDA-MB231 cells; Figure S5. Histograms of (A) MDA-MB231 cells stained with propidium iodide and after being treated with (B) Nano-Veh; (C) Nic; (D) Nic-Veh and (E) CD44-Nic-Veh; Figure S6. H&E performed on tumor cross sections from animals treated with (A, B) NIC-Veh and (C, D) CD44-NIC-Veh; Figure S7. Immuno-histochemistry performed on tumor cross sections from animals treated with (A, B) CD44-NIC-Veh and (C, D) NIC-Veh; Figure S8. Expression of 'stem-ness genes' namely CD44, CD24, PROM1, LIN28A, LIN28B, ALDH1A1, POU5F1, NOTCH1, SOX2, CTGF, MMP1, EPCAM, FGFR1, ERBB2, CXCR4, PROCR, TGFB1, CTNNB1, WNT1 and WNT2 studied in control tumors and tumors treated with CD44-NIC-Veh.

Cancer stem cells are known to be controlled by pathways that are dormant in normal adult cells, for example, PTEN, which is a negative regulator of transcription factor STAT3. STAT3 regulates genes that are involved in stem cell self-renewal and thus represents a novel therapeutic target of enormous clinical significance. Studies on breast cancer stem cells (BCSC) have been also significantly correlated with STATs. We describe here for the first time a novel strategy to selectively target CSCs and to induce downregulation of STAT3 downstream target genes reducing expression of series of “stem-ness genes” in treated tumors. In vitro and in vivo experiments were performed to evaluate functional activity with gene and protein expression studies. The results of the study indicate that this targeted delivery approach deactivates STAT3 causing a reduction of CD44+/CD24− CSC populations with aptly tracked gene and protein regulations of “stemness” characteristics. Mol Cancer Ther; 17(1); 119–29. ©2017 AACR.

Gastrointestinal (GI) tract is one of the hard-to-reach target tissues for the delivery of contrast agents and drugs mediated by nanoparticles due to its harsh environment. Herein, we overcame this barrier by designing orally ingestible probiotic vectors for 'hitchhiking' ultrasmall hafnia (HfO

A new pH-responsive cationic co-liposomal formulation was prepared in this study using the twin version of the amphiphile palmitoyl homocysteine, TPHC; natural zwitterionic lipid, DOPE; and cholesterol-based twin cationic lipid, C5C, at specified molar ratios. This co-liposome was further decorated with a newly designed fluorescently tagged, cholesterol-tethered EpCAM-targeting RNA aptamer for targeted gene delivery. This aptamer-guided nanoliposomal formulation, C5C/DOPE/TPHC at 8:24:1 molar ratio, could efficiently transport the genes in response to low pH of cellular endosomes selectively to the EpCAM overexpressing cancer stem cells. This particular observation was extended using siRNA against GFP to validate their transfection capabilities in response to EpCAM expression. Overall, the aptamer-guided nanoliposomal formulation was found to be an excellent transfectant for in vitro siRNA gene delivery.

A liposomal formulation comprising a dicationic cholesterol based lipid, Chol+-(CH2)5-Chol+ and a helper, zwitterionic lipid, DOPE (1:4) was prepared to deliver polynucleotides of different topolog...

By using complementary DNA sequences as surface ligands, we selectively allow two individual diffusing "dual-color" carbon dots to interact in situ and in vitro. Spontaneous nanoscale oxidation of surface-abundant nitroso-/nitro-functionalities leads to two distinctly colored carbon dots (CD) which are isolated by polarity driven chromatographic separation. Green- and red-emitting carbon dots (gCD and rCD) were decorated by complementary single-stranded DNAs which produce a marked increase in the fluorescence emission of the respective carbon dots. Mutual colloidal interactions are achieved through hybridization of complementary DNA base pairs attached to the respective particles, resulting in quenching of their photoluminescence. The observed post-hybridization quenching is presumably due to a combined effect from an aggregation of CDs post duplex DNA formation and close proximity of multicolored CDs, having overlapped spectral regions leading to a nonradiative energy transfer process possibly released as heat. This strategy may contribute to the rational design of mutually interacting carbon dots for a better control over the resulting assembly structure for studying different biological phenomenon including molecular cytogenetics. One of the newly synthesized CDs was successfully used to image intracellular location of GAPDH mRNA using an event of change in fluorescence intensity (FI) of CDs. This selectivity was introduced by conjugating an oligonucleotide harboring complementary sequence to GAPDH mRNA. FI of this conjugated carbon dot, rCD-GAPDH, was also found to decrease in the presence of Ca2+, varied in relation to H+ concentrations, and could serve as a tool to quantify the intracellular concentrations of Ca2+ and pH value (H+) which can give important information about cell survival. Therefore, CD-oligonucleotide conjugates could serve as efficient probes for cellular events and interventions.

In recent times, the world is changing and gearing up with latest and new technologies in that scenario the development and growth of the composite materials is increasing day by day. Natural fibres are one of the realistic and ecological alternatives to synthetic fibres as reinforcement for polymer composite materials due to their low cost, environmental friendliness, natural abundance, and mechanical properties. Natural fibres are given first priority compared all types of fibres because of their attractive characteristics such as biodegradable nature, low cost, ecofriendly and good strength to weight ratio in the engineering products and minimal health hazards. An overview on the recent trends in the physio-mechanical properties, thermal properties, electrical properties such as dielectric constant, microstructural interfacial adhesion, different methods used for the fabrication of the natural fiber polymer composites and their respective applications of NFPC’s has been discussed thoroughly in this critical review. According to the literature survey, the various work has carried out on the natural fibers which shows its importance comparatively with the other synthetic fibers. This review states the potential of natural fibre which can be used to reinforce the polymer matrix for several applications such as sports goods, electrical and electronics, automotive, construction industry etc.

Carbon materials are generally utilized in the form of carbon allotropes and their characteristics are exploited as such or for improving the thermal, electrical, optical, and mechanical properties of other biomaterials. This has now found a broader share in conventional biomaterial space with the generation of nanodiamond, carbon dot, carbon nanoparticles (CNPs), and so forth. With properties of better biocompatibility, intrinsic optical emission, aqueous suspendability, and easier surface conjugation possibilities made CNPs as one of the fore most choice for biological applications especially for use in intracellular spaces. There are various reports available presenting methods of preparing, characterizing, and using CNPs for various biological applications but a collection of information on what makes CNP a suitable biomaterial to achieve those biological activities is yet to be provided in a significant way. Herein, a series of correlations among synthesis, characterization, and mode of utilization of CNP have been incorporated along with the variations in its use as agent for sensing, imaging, and therapy of different diseases or conditions. It is ensembled that how simplified and optimized methods of synthesis is correlated with specific characteristics of CNPs which were found to be suitable in the specific biological applications. These comparisons and correlations among various CNPs, will surely provide a platform to generate new edition of this nanomaterial with improvised applications and newer methods of evaluating structural, physical, and functional properties. This may ensure the eventual use of CNPs for human being for specific need in near future. This article is categorized under: Nanotechnology Approaches to BiologyNanoscale Systems in Biology Diagnostic ToolsBiosensing Diagnostic ToolsIn Vitro Nanoparticle-Based Sensing Therapeutic Approaches and Drug DiscoveryEmerging Technologies.

As far back as the industrial revolution, significant development in technical innovation has succeeded in transforming numerous manual tasks and processes that had been in existence for decades where humans had reached the limits of physical capacity. Artificial Intelligence (AI) offers this same transformative potential for the augmentation and potential replacement of human tasks and activities within a wide range of industrial, intellectual and social applications. The pace of change for this new AI technological age is staggering, with new breakthroughs in algorithmic machine learning and autonomous decision-making, engendering new opportunities for continued innovation. The impact of AI could be significant, with industries ranging from: finance, healthcare, manufacturing, retail, supply chain, logistics and utilities, all potentially disrupted by the onset of AI technologies. The study brings together the collective insight from a number of leading expert contributors to highlight the significant opportunities, realistic assessment of impact, challenges and potential research agenda posed by the rapid emergence of AI within a number of domains: business and management, government, public sector, and science and technology. This research offers significant and timely insight to AI technology and its impact on the future of industry and society in general, whilst recognising the societal and industrial influence on pace and direction of AI development.

Photoacoustic imaging has emerged as a promising imaging platform with a high tissue penetration depth. However, biodegradable nanoparticles, especially those for photoacoustic imaging, are rare and limited to a few polymeric agents. The development of such nanoparticles holds great promise for clinically translatable diagnostic imaging with high biocompatibility. Metabolically digestible and inherently photoacoustic imaging probes can be developed from nanoprecipitation of biliverdin, a naturally occurring heme-based pigment. The synthesis of nanoparticles composed of a biliverdin network, cross-linked with a bifunctional amine linker, is achieved where spectral tuning relies on the choice of reaction media. Nanoparticles synthesized in water or water containing sodium chloride exhibit higher absorbance and lower fluorescence compared to nanoparticles synthesized in 2-(N-morpholino) ethanesulfonic acid buffer. All nanoparticles display high absorbance at 365 and 680 nm. Excitation at near-infrared wavelengths leads to a strong photoacoustic signal, while excitation with ultraviolet wavelengths results in fluorescence emission. In vivo photoacoustic imaging experiments in mice demonstrated that the nanoparticles accumulate in lymph nodes, highlighting their potential utility as photoacoustic agents for sentinel lymph node detection. The biotransformation of these agents was studied using mass spectroscopy, and they were found to be completely biodegraded in the presence of biliverdin reductase, a ubiquitous enzyme found in the body. Degradation of these particles was also confirmed in vivo. Thus, the nanoparticles developed here are a promising platform for biocompatible biological imaging due to their inherent photoacoustic and fluorescent properties as well as their complete metabolic digestion.

Effective outcome from dynamic live-cell-imaging requires utilization of a probe with high emission intensity and low photobleaching. It would be preferable to achieve such properties at a low power of the applied laser to avoid any probable damage to biological cells or tissue. Most of the used small-molecule fluorophores have been reported to show significant photobleaching in a time-dependent manner and require high laser power to gain significant intensity for bioimaging. Carbon nanoparticles have recently been successfully used for cell imaging with low bleaching characteristics but require high laser power and lack optical nonlinearity at low power levels. Here, we report the preparation, characterization, and application of a Nanoscale Carbon (NC) which, on being surface decorated with crescent-shaped poly-lysine (PLNC), provides two-photon fluorescence (TPF) and low bleaching properties. PLNC was found to stain the cytoplasm of C2C12 muscle cells in the first four-hours of incubation with high TPF in the infrared range and can be useful for deep tissue imaging with further improvements.

Sarcomas are rare and heterogeneous cancer variants of mesenchymal origin. Their genetic heterogeneity coupled with uncertain histogenesis makes them difficult to treat and results in poor prognosis. In this work, we show that structure-based drug discovery involving computational modeling can be used to identify a new retinoid X receptor (RXR) agonist ligand with a bis(indolyl)methane scaffold. This agent co-self-assembles with an amphiphilic diblock copolymer resulting in nanoparticles (Nano-RXR) with excellent kinetic stability, which were evaluated for efficacy and safety in transformed sarcoma cells, 63-3 Cre and 141-10 Cre of pig origin, and in rodent xenograft models. Responses at gene and protein levels established the treatment approach as a highly effective RXR agonist across cell, rodent, and "Oncopig" models. Interestingly, Nano-RXR was not only able to modulate metabolic and transporter genes related to orphan nuclear receptors but also played a major role in modulating programmed cell death in sarcomas developed in Oncopigs.

Targeting the DNA of tumor cells with small molecules may offer effective clinical strategies for transcriptional inhibition. We unveil synthesis and characterization of ∼20 nm chiral carbon nanoparticles for enantiospecific recognition of DNA. Our approach inculcates chirality in carbon nanoparticles by controlled tethering of minor groove binders, i.e., Tröger's base (TB). The chiral particles positively enriched the cellular nucleus in MCF-7 breast cancer cells, irrespective of the TB asymmetry tethered on the particle surface, but negatively induced chiral carbon nanoparticles exhibited improved efficiency at inhibiting cell growth. Further studies indicated that these chiral particles act as nanotweezers to perturb the genomic DNA and induce apoptosis cascade in cancer cells.

Ocular drug delivery has always been a challenging feat to achieve in the field of medical sciences. One of the existing methods of non-invasive ocular drug delivery is the use of eye drops. However, drugs administered through these formulations have low bioavailability in the ocular system. This limitation can been overcome by using contact lenses as drug delivery vehicles. According to USA FDA definitions they can be categorized into two main categories-hard and soft contact lenses. Based on the material properties, hard contact lenses are mostly produced from polymers of acrylate monomers such as MMA (methyl methacrylate). These have the least water retention capacity, thereby, having minimal ability to diffuse oxygen into the corneal layer and are not ideal for long term use. Soft material contact lenses are flexible and are mainly hydrogel based. They have higher water retention capacities as compared to rigid contact lenses, which gives them the ability to transmit oxygen to the corneal layer. These hydrogel based soft materials are mainly produced from polymers of acrylate monomers such as HEMA (hydroxyethyl methacrylate) and found to be better for drug delivery contact lenses. These polymer-based soft materials have been efficiently modified in terms of their chemistry to achieve diverse physicochemical properties to produce efficient ocular drug delivery systems. However, complications such as drug leaching during storage and distribution, sterilisation, preservation of integrity of the lens and the possibility of surface roughness due to the incorporated drug molecules still need to be optimised. This review highlights the chemistries of various polymeric molecules through which physicochemical properties can be modified to achieve optimum drug loading and sustained release of the drug for application in the ocular system.

Lipoplex nano-aggregates have been analyzed through biophysical characterization (electrostatics, structure, size and morphology), and biological studies (transfection efficiency and cell viability) in five cancer cell lines. Lipoplexes were prepared from pEGFP-C3 plasmid DNA (pDNA) and mixed liposomes, constituted by a zwitterionic lipid (DOPE) and a gemini cationic lipid (GCL) synthesized in this work, [bis(hexadecyl dimethyl ammonium) oxyethylene], referred to as (C16Am)2(C2O)n, (where n is the oxyethylene spacer length, n = 1, 2 or 3, between the ammonium heads). Cryo-TEM micrographs show nano-aggregates with two multilamellar structures, a cluster-type (at low-to-medium GCL composition) and a fingerprint-type that coexists with the cluster-type at medium GCL composition and appears alone at high GCL composition. SAXS diffractograms show that these lipoplexes present three lamellar structures, two of them coexisting at low and high GCL composition. The optimized transfection efficiency (TE) of pDNA was higher for lipoplexes containing GCLs with a longer (n = 3) or shorter (n = 1) polyoxyethylene spacer, at high GCL composition (α = 0.7) with low charge ratio (ρeff = 2). In the all cancer cell lines studied, the TE of the optimized formulations was much better than those of both lipofectamine 2000 and lipoplexes with GCLs of the bis(hexadecyl dimethyl ammonium) alkane series recently reported. Probably, (a) the coexistence of two lamellar structures at high GCL composition synergizes the TE of these lipid vectors, (b) the orientation of the polyoxyethylene region in (C16Am)2(C2O)3/DOPE may occur in such a way that the spacing between two cationic heads becomes smaller than that in (C16Am)2(C2O)2/DOPE which is poor in terms of TE, and (c) the synergistic interactions between serum proteins and (C16Am)2(C2O)n/DOPE-pDNA lipoplexes containing a polyoxyethylene spacer improve TE, especially at high GCL content. Lipoplexes studied here show very low levels of toxicity, which confirm them as improved vectors of pDNA in gene therapy.

Artificial Intelligence (AI) usage is rapidly expanding in our society. Private sector has already taken the leap of faith in using AI for efficiency and for generating better value for the customers and shareholders. The promise of AI is quite alluring for the governments as well. It promises to be the breakthrough technology which can catapult public sector to hitherto unseen efficiency and productivity. It has the potential to truly transform the public service delivery and the way government interfaces with citizens – from a demand driven model to a predictive model of public service delivery. However, there are a large number of pitfalls and blind-spots associated with AI, which make its adoption in government particularly challenging. For successful adoption of AI in public sector, governments must understand these challenges clearly and lay down regulatory public policies to ensure that the possible adverse impacts (such as exclusion, bias etc.) of AI are mitigated. This paper attempts to systematically explore these challenges with a view to enable public policy makers to respond to them.

Although significant technological advancements have been made in the development of analytical biosensor chips for detecting bacterial strains (E. coli, S. Mutans and B. Subtilis), critical requirements i.e. limit of detection (LOD), fast time of response, ultra-sensitivity with high reproducibility and good shelf-life with robust sensing capability have yet to be met within a single sensor chip. In order to achieve these criteria, we present an electrically-receptive thermally-responsive (ER-TR) sensor chip comprised of simple filter paper used as substrate coated with composite of poly(N-isopropylacrylamide) polymer (PNIPAm) - graphene nanoplatelet (GR) followed by evaporation of Au electrodes for capturing both Gram-positive (S. mutans and B. subtilis) and Gram-negative (E. coli) bacterial cells in real-time. Autoclave water, tap water, lake water and milk samples were tested with ER-TR chip with and without bacterial strains at varying concentration range 101-105 cells/mL. The sensor was integrated with in-house built printed circuit board (PCB) to transmit/receive electrical signals. The interaction of E. coli, S. mutans and B. subtilis cells with fibers of PNIPAm-GR resulted in a change of electrical resistance and the readout was monitored wirelessly in real-time using MATLAB algorithm. Finally, prepared ER-TR chip exhibited the reproducibility of 85-97% with shelf-life of up to four weeks after testing with lake water sample.

Phosphonated compounds, in particular, bisanalogs are widely applied in clinical settings for the treatment of severe bone turnovers and recently as imaging probes when conjugated with organic fluorophores. Herein, we introduce a bone seeking luminescent probe that shows a high binding affinity toward bone minerals based on monophosphonated carbon dots (CDs). Spheroidal CDs tethered with PEG monophosphates are synthesized in a one-pot hydrothermal method and are physicochemically characterized, where the retention of phosphonates is confirmed by 13P NMR and X-ray photoelectron spectroscopy. Interestingly, the high abundance of multiple monodentate phosphonates exhibited strong binding to hydroxyapatite, the main bone mineral constituent. The remarkable optophysical properties of monophosphonated CDs were confirmed in an ex vivo model of the bovine cortical bone where the imaging feasibility of microcracks, which are calcium-rich regions, was demonstrated. The in vivo studies specified the potential application of monophosphonated CDs for imaging when injected intramuscularly. The biodigestible nature and cytocompatibility of the probe presented here obviate the demand for a secondary fluorophore, while offering a nanoscale strategy for bone targeting and can eventually be employed for potential bone therapy in the future.

A major proportion of basic cause for human cancer has been linked to widespread environmental pollutants including analogs of polyarenes. Search of an effective therapy can be started with the understanding of the generation of such "carcinogens" and their biological interactions. This review is to discuss the syntheses, structural activities, mechanistic and biological studies of polyarenes such as polycyclic aromatic hydrocarbons (PAHs), polycyclic azaarenes (PAAs) and their thia-analogs (PASH). It also summarizes the mechanism of mutagenicity and tumorigenicity via metabolic interventions producing diol epoxide complexes and eventually formation of DNA adducts. It suggests that inhibition of oxidative reactions and formation of diols and epoxides and unspecific intracellular activation of cytochrome P450 enzymes could be approaches in therapy against such mutagenicity and tumorigenicity. Thus, this review reflects that understanding of molecular mechanisms and activations along with a clinical and translational medicine approach would require achieving both prevention and treatment of this atrocity.

Prostate-specific antigen (PSA) is a commonly used biomarker for the detection of prostate cancer (PCa) and there are numerous data available for its invasive detection in the serum and whole blood. In this work, an electrochemical sensing method was devised to detect traces of PSA in human saliva using a hybrid nanocomposite of graphene nanoplatelets with diblock co-polymers and Au electrodes (GRP-PS67-b-PAA27-Au). The pure graphitic composition on filter paper provides significantly high electrical and thermal conductivity while PS67-b-PAA27 makes an amphiphilic bridge between GRP units. The sensor utilizes the binding of an anti-PSA antibody with an antigen-PSA to act as a resistor in a circuit providing an impedance change that in turn allows for the detection and quantification of PSA in saliva samples. A miniaturized electrical impedance analyzer was interfaced with a sensor chip and the data were recorded in real-time using a Bluetooth-enabled module. This fully integrated and optimized sensing device exhibited a wide PSA range of detection from 0.1 pg mL-1 to 100 ng mL-1 (R2 = 0.963) with a lower limit of detection of 40 fg mL-1. The performance of the biosensor chip was validated with an enzyme-linked immunosorbent assay technique with a regression coefficient as high as 0.940. The advantages of the newly developed saliva-PSA electrical biosensor over previously reported serum-PSA electrochemical biosensors include a faster response time (3-5 min) to achieve a stable electrical signal for PSA detection, high selectivity, improved sensitivity, no additional requirement of a redox electrolyte for electron exchange and excellent shelf life. The presented sensor is aimed for clinical commercialization to detect PSA in human saliva.

Emerging chemical contaminants such as pharmaceutical residues in water resources continue to threaten the homeostasis of our ecosystem. We have developed a ‘smart-filter’ comprising tunable, biodegradable, and commercially amenable pharmaceutical-nano-carbon-scavengers (PNCSs) to efficiently and safely remediate pharmaceutical residues. The PNCS particles successfully removed 63.5 ± 0.4% of carbamazepine, 99.76 ± 0.01% of gemfibrozil and >99.9% of triclocarban from a mixture containing 0.2 μg L−1 of each by merely using 0.5 mg mL−1 of PNCS, thus out-performing commonly used scavengers.

Host defense peptides (HDPs) are a class of evolutionarily conserved substances of the innate immune response that have been identified as major players in the defense system in many living organisms. Some of the HDPs are also referred to as peptidotoxins, which offer immense potential for anticancer therapy. However, their therapeutic potential is yet to be fully translated mainly due to their off-target toxicity. Here we show that their nanoenabled delivery may become beneficial in controlling their delivery in intracellular space. We introduced an amphiphilic polymer to synthesize a well-defined, self-assembled, rigid-cored polymeric nanoarchitecture for controlled delivery of three model peptidotoxins, i.e., melittin, TSAP-1, and a negative control peptide of synthetic origin. Interestingly, our results revealed strong interaction of peptidotoxins with duplex plasmid DNA. Extensive biophysical characterization (UV-vis spectroscopy, gel electrophoresis, MTT assay, and flow assisted cell sorting) experimentally verified that peptidotoxins were able to interact with genomic DNA in vitro and in turn influence the cancer cell growth. Thus, we unraveled that, through genomic DNA regulation, peptidotoxins can play a role in cell cycle regulation and exert their anticancer activities.

Relationship of the surface physicochemical characteristics of nanoparticles with their interactions with biological entities may provide critical information for nanomedicinal application. Here, we report the systematic synthesis of sub-50 nm carbon nanoparticles (CNP) presenting neutral, anionic, and cationic surface functionalities. A subset of CNPs with ~10, 20, and 40 nm hydrodynamic sizes were synthesized with neutral surface headgroups. For the first time, the cellular internalization of these CNPs was systematically quantified in various stages of breast cancer cells (early, late, and metastatic), thereby providing a parametric assessment of charge and size effects. Distinct activities were observed when these systems interacted with cancer cells in various stages. Our results indicated that metastatic breast cancer could be targeted by a nanosystem presenting anionic phosphate groups. On the contrary, for patients in late stage of cancer, drugs could be delivered with sulfonate functionalized carbon nanoparticles, which have higher probability of intracellular transport. This study will facilitate the better understanding of nanoparticle–biological entity interaction, and the integration of this knowledge with pathophysiology would promote the engineering of nanomedicine with superior likelihoods of crossing the endocytic “barrier” for drug delivery inside cancerous cells.

Reversible switching of photoluminescence (PL) of carbon nanoparticles (CNP) can be achieved with counterionic macromolecular caging and decaging at the nanoscale. A negatively charged uncoated, "bare" CNP with high luminescence loses its PL when positively charged macromolecules are wrapped around its surface. Prepared caged carbons could regain their emission only through interaction with anionic surfactant molecules, representing anionic amphiphiles of endocytic membranes. This process could be verified by gel electrophoresis, spectroscopically and in vitro confocal imaging studies. Results indicated for the first time that luminescence switchable CNPs can be synthesized for efficient intracellular tracking. This study further supports the origin of photoluminescence in CNP as a surface phenomenon correlated a function of characteristic charged macromolecules.

Transcription factor STAT3 has been shown to regulate genes that are involved in stem cell self-renewal and thus represents a novel therapeutic target of great biological significance. However, many small molecule agents with potential effects in cancer therapy lack aqueous solubility and high off-target toxicity, hence impeding efficient bioavailability and activity. This work, for the first time, reports a prodrug-based strategy for selective and safer delivery of STAT3 inhibitors designed towards metastatic and drug resistant breast cancer. We have synthesized a novel lipase-labile SN-2 phospholipids-pro-drug from a clinically investigated STAT3 inhibitor, nifuroxazide (Pro-nifuroxazide), which can be regioselectively cleaved by the membrane abundant enzymes in cancer cells. Pro-nifuroxazide self-assembled to sub 20 nm nanoparticles and the cytotoxic ability was screened in ER (+)-MCF-7 and ER(−)-MD-MB231 cells at 48–72h using MTT proliferation assay. Results indicated that pro-nifuroxazide NP are multifold more effective towards inhibiting cancer cells in a time dependent manner compared to parent nifuroxazide. A remarkable improvement in the local concentration of drug to as high as ~240 folds when assembled into nanoparticles is presumably the reason for this functional improvement. We introduced molecular dynamics (MD) simulations to generate Pro-nifuroxazide nano-assembly, a model assembly from triggerable anti-cancer drug, to provide molecular insights correlating physico-chemical and anti-cancer properties. In silico properties of Pro-nifuroxazide including size and chemistry of nanoparticles and membrane interactions with individual molecules could be validated by in vitro functional activities in cells of breast cancer origin. The in vivo anti-cancer efficiencies of Pro-nifuroxazide nanoparticles in nude mice xenografts with MCF-7 revealed remarkable growth inhibition as high as 400% for Pro-nifuroxazide nanoparticle. Histopathological analysis corroborated these findings showing significantly high nuclear fragmentation and retracted cytoplasm. Immuno-staining on tumor section demonstrated significantly lower level of pSTAT-3 by Pro-nifuroxazide nanoparticle treatment establishing the inhibition of STAT-3 phosphorylation. Our strategy for the first time proposes a translatable prodrug agent self-assembled into nanoparticles and demonstrate remarkable enhancement in IC(50), induced apoptosis and reduced stem like cancer cell population through STAT-3 inhibition and reduced phosphorylation.

In this work, an ultra-sensitive electrochemical-digital sensor chip is devised for potential use as a digital stress analyzer for point-of-care testing (POCT) and preventive on-site recording of the hormone 'cortisol', a glucocorticoid class of steroid hormone present in the human saliva. The sensor was interfaced and re-configured with a high precision impedance converter system (AD5933) and used for electrochemical impedance spectroscopy (EIS) to evaluate the cortisol levels in seven saliva samples. To obtain enhanced biological (cortisol) recognition and achieve a lower limit of detection 0.87 ± 0.12 pg mL-1 (2.4 ± 0.38 pmol mL-1) with a wide range from 1 pg mL-1 to 10 ng mL-1 (2.75 pmol mL-1 to 27.58 pmol mL-1; R2 = 0.9831), bovine serum albumin (1% BSA) was utilized as an effective sensitivity enhancer in addition to optimizing the other two parameters: (i) anti-cortisol antibody (anti-CAb) covalently attached to micro-Au electrodes and (ii) saliva sample incubation time on the sensor chip. The results obtained in this work were corroborated with the gold standard ELISA test with an accuracy of 96.3% and other previously reported biosensors. We envisage that the conceivable standpoint of this study can be a practice towards new development in cortisol biosensing, which will be pertinent to POCT targeted for in vitro psychobiological study on patient cortisol in saliva, and finally an implantable sensor chip in the future.

The blockchain has received significant attention from technology focussed researchers, highlighting its perceived impact and emerging disruption potential, but has been slow to engender any significant momentum within the Information Systems (IS) and Information Management (IM) literature. This study approaches the subject through an IS/IM lens developing the key themes from the blockchain based research via a comprehensive review. This analysis of the body of literature highlights that although few commercial grade blockchain applications currently exist, the technology demonstrates significant potential to benefit a number of industry wide use cases. This study expands on this point articulating through each of the key themes to develop a detailed narrative on the numerous potential blockchain applications and future direction of the technology, whilst discussing the many barriers to adoption. The study asserts that blockchain technology has the potential to contribute to a number of the UN Sustainability Development Goals and engender widespread change within a number of established industries and practices.

In sixty-five years, merely nine percent of plastic waste was recycled and reused, twelve percent was incinerated, and the remaining seventy-nine percent has built up in landfills or ended up elsewhere in the environment. Statistically, the remaining seventy-nine percent of plastic wastes can be recycled in more than five-hundred years. Building and construction material is expensive due to the demand of the growing population with a low supply of the materials. To address this, the usage of solid-wastes for the manufacture of bricks and other building materials is an ideal-optimal approach towards tackling the challenges of handling waste-products as well as optimizing the production-cost of construction materials. Subsequently, plastic bottles, plastic containers, and plastic bags are flexible and possesses several characteristics includes good versatility, hardness, lightness, and resistance to chemicals and water and impact which can be heated and reshape to form a building material. Thus, this review briefly focusses on the possibility of utilizing non-hazardous wastes such as plastic wastes, glass bottles, and other solid-industrial wastes in making effective and quality and sand brick as substitute for expensive building material. This study is also aimed at educating the engineering public and professionals on the importance and necessity of waste management, reuse and recycling and also awareness on the benefits of conserving our environment through the reuse and utilization of waste within it. The review helps to identify the different types of wastes with potential of utilization towards construction and several key research factors and criteria which can provide focus and direction towards the choice of wastes-type to be used and ensuring that they have utilization potentials in the various value-addition applications. The piling of such wastes poses an environmental problem often on account of chemicals which the ecosystem has never been used to. These affect its proper functioning and in turn at the global level, are likely to affect even the stability of biosphere. The pool of information on Solid Wastes generation, disposal and management is increasing each year. A comprehensive review of available literature regarding Solid Wastes generation, disposal and management has been presented in this article.

The COVID-19 pandemic has forced many organisations to undergo significant transformation, rethinking key elements of their business processes and use of technology to maintain operations whilst adhering to a changing landscape of guidelines and new procedures. This study offers a collective insight to many of the key issues and underlying complexities affecting organisations and society from COVID-19, through an information systems and technological perspective. The views of 12 invited subject experts are collated and analysed where each articulate their individual perspectives relating to: online learning, digital strategy, artificial intelligence, information management, social interaction, cyber security, big data, blockchain, privacy, mobile technology and strategy through the lens of the current crisis and impact on these specific areas. The expert perspectives offer timely insight to the range of topics, identifying key issues and recommendations for theory and practice.

Spatial and spectral information of a nanocarrier and its payload is crucial for the advancement of luminescence-based imaging, disease detection, and treatment in complex biological environment. However, it remains challenging to track and quantify the delivery and localization of drugs lacking inherent fluorescence. It is demonstrated that sub 30 nm phospholipid-stabilized nanoparticles can be detected and quantified using hyperspectral transmitted light microscopy without using a fluorophore. In two proposed model systems, phospholipid-passivated carbon nanoparticles incorporate the drug in either free form or as a lipid-based prodrug. Following a rigorous characterization of these nanoparticles, in vitro toxicities via loss in cell growth density and mitochondrial respiration is studied in MCF-7 breast cancer cells. Furthermore, a detailed inhibitor based study reveals that these particles are internalized based on a clathrin-mediated pathway, irrespective of the choice of drug formulation. Hyperspectral imaging is performed to obtain the colocalization of carbon nanoparticles and drug molecules intracellularly and can successfully be tracked while therapeutic release is quantified in 3D space. The present work demonstrates that nanoparticles and therapeutic agents can be mapped and measured simultaneously barring the requirement of a dye, thus providing new avenues in the spatiotemporal characterization and synchronous detection and quantification of payload and carrier.