Suitably Incorporated Hydrophobic, Redox-Active Drug in Poly Lactic Acid-Graphene Nanoplatelet Composite Generates 3D-Printed Medicinal Patch for Electrostimulatory Therapeutics.

Polymer carbon composites have been reported for improved mechanical, thermal and electrical properties to provide reduced side effect by 3D printing personalized biomedical drug delivery devices. But control on homogeneity in loading and release of dopants like carbon allotropes and drugs, respectively, in the bulk and on the surface has always been a challenge. Herein, we are reporting a methodological cascade to achieve a model, customizable, 3D printed, homogeneously layered and electrically stimulatory, PLA-Graphene nanoplatelet (hl-PLGR) based drug delivery device, called 3D-est-MediPatch. The medicinal patch has been prepared by 3D-printing a Nic-hl-PLGR composite obtained by incorporating a redox active model drug, niclosamide (Nic) in hl-PLGR. The composite of Nic-hl-PLGR was characterized in three sequentially complex forms─composite film, hot melt extruded (HME) filament, and 3D printed (3DP) patches to understand the effect of filament extrusion and 3D-printing processes on Nic-hl-PLGR composite and overall drug incorporation efficiency and control. The incorporation of graphene was found to improve the homogeneity of the drug, and the hot melt extrusion improved the dispersion of drug and graphene fillers in the composite. The electroresponsive drug release from the Nic-hl-PLGR composite was found to be controllably accelerated compared to the drug release by diffusion, in simulated buffer condition. The released drug concentration was found to reach within the IC50 range for malignant melanoma cell (A375) and showed in vitro selectively, with reduced effects in noncancerous, fibroblast cells (NIH3T3). Further, the feasibility of application for this system was assessed in generating personalized 3D-est-MediPatch for skin, liver and spleen tissues in ex-vivo scenario. It showed excellent feasibility and efficacy of the 3D-est-MediPatch in controlled and personalized release of drugs during electrostimulation. Thus, a model platform, 3D-est-MediPatch, could be achieved by suitably incorporating a hydrophobic, redox-active drug (niclosamide) in poly lactic acid-graphene nanoplatelet composite for electrostimulatory therapeutics with reduced side effects.

Remediation of pharmacophoric laboratory waste by using biodegradable carbon nanoparticles of bacterial biofilm origin.

Research laboratories generate a broad range of hazardous pharmacophoric chemical contaminants, from drugs to dyes used during various experimental procedures. In the recent past, biological methods have demonstrated great potential in the remediation of such contaminants. However, the presence of pharmacophoric chemicals containing antibiotics, xenobiotics, and heavy metals suppresses the growth and survivability of used microbial agents, thus decreasing the overall efficiency of biological remediation processes. Bacterial biofilm is a natural arrangement to counter some of these inhibitions but its use in a systemic manner, portable devices, and pollutant remediation plants post serious challenges. This could be countered by synthesizing a biodegradable carbon nanoparticle from bacterial biofilm. In this study, extracellular polymeric substance-based carbon nanoparticles (Bio-EPS-CNPs) were synthesized from bacterial biofilm derived from Bacillus subtilis NCIB 3610, as a model bacterial system. The produced Bio-EPS-CNPs were investigated for physiochemical properties by dynamic light scattering, optical, Fourier-transformed infrared, and Raman spectroscopy techniques, whereas X-ray diffraction study, scanning electron microscopy, and transmission electron microscopy were used to investigate structural and morphological features. The Bio-EPS-CNPs exhibited negative surface charge with spherical morphology having a uniform size of sub-100 nm. The maximum remediation of some laboratory-produced pharmacophoric chemicals was achieved through a five-round scavenging process and confirmed by UV/Vis spectroscopic analysis with respect to the used pharmacophore. This bioinspired remediation of used pharmacophoric chemicals was achieved through the mechanism of surface adsorption via hydrogen bonding and electrostatic interactions, as revealed by different characterizations. Further experiments were performed to investigate the effects of pH, temperature, stirring, and the protocol of scavenging to establish Bio-EPS-CNP as a possible alternative to be used in research laboratories for efficient removal of pharmacophoric chemicals by incorporating it in a portable, filter-based device.

Orthogonal self-assembly of an organoplatinum(II) metallacycle and cucurbit[8]uril that delivers curcumin to cancer cells.

Curcumin (Cur) is a naturally occurring anticancer drug isolated from the Curcuma longa plant. It is known to exhibit anticancer properties via inhibiting the STAT3 phosphorylation process. However, its poor water solubility and low bioavailability impede its clinical application. Herein, we used organoplatinum(II) ← pyridyl coordination-driven self-assembly and a cucurbit[8]uril (CB[8])-mediated heteroternary host-guest complex formation in concert to produce an effective delivery system that transports Cur into the cancer cells. Specifically, a hexagon 1, containing hydrophilic methyl viologen (MV) units and 3,4,5-Tris[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]benzoyl groups alternatively at the vertices, has been synthesized and characterized by several spectroscopic techniques. The MV units of 1 underwent noncovalent complexation with CB[8] to yield a host-guest complex 4. Cur can be encapsulated in 4, via a 1:1:1 heteroternary complex formation, resulting in a water-soluble host-guest complex 5. The host-guest complex 5 exhibited ca 100-fold improved IC50 values relative to free Cur against human melanoma (C32), melanoma of rodents (B16F10), and hormone-responsive (MCF-7) and triple-negative (MDA-MB231) breast cancer cells. Moreover, strong synergisms of Cur with 1 and 4 with combinatorial indexes of <1 across all of the cell lines were observed. An induced apoptosis with fragmented DNA pattern and inhibited expression of phosphor-STAT3 supported the improved therapeutic potential of Cur in heteroternary complex 5.

Enhancing disease resistance in poplar through modification of its natural defense pathway.

KEY MESSAGE: Modification of the poplar defense pathway through pathogen-induced expression of an amphibian host defense peptide modulates plant innate immunity and confers robust and reliable resistance against a major poplar pathogen, Septoria musiva. Host defense peptides (HDPs), also known as cationic antimicrobial peptides, represent a diverse group of small membrane-active molecules that are part of the innate defense system of their hosts against pathogen invasion. Here we describe a strategy for development of poplar plants with enhanced HDP production and resistance to the commercially significant fungal pathogen Septoria musiva. The naturally occurring linear amphipathic α-helical HDP dermaseptin B1, which has 31 residues and originated from the skin secretion of arboreal frogs, was N-terminally modified (MsrA2) and evaluated in vitro for antifungal activity and phytotoxicity. The MsrA2 peptide inhibited germination of S. musiva conidia at physiologically relevant low micromolar concentrations that were non-toxic to poplar protoplasts. The nucleotide sequence of MsrA2, optimized for expression in plants, was introduced into the commercial hybrid poplar Populus nigra L. × P. maximowiczii A. Henry (NM6) via Agrobacterium-mediated transformation. Transgene expression was regulated by the pathogen-inducible poplar promoter win3.12T, a part of the poplar innate defense system. Most importantly, the induced accumulation of MsrA2 peptide in poplar leaves was sufficient to confer resistance against S. musiva. The antifungal resistance of plants with high MsrA2 expression and MsrA2 accumulation was strong and reproducible, and without deleterious effects on plant growth and development. These results provide an insight into development of new technologies for engineering durable disease resistance against major pathogens of poplar and other plants.

Electrochemical-digital immunosensor with enhanced sensitivity for detecting human salivary glucocorticoid hormone.

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.

Correction to: Spatiotemporal activities of Douglas-fir BiP Pro1 promoter in transgenic potato.

In Table 1, the unit of measure provided for GUS activity in unstressed leaves was not given correctly in the original publication. It should read.

Spatiotemporal activities of Douglas-fir BiP Pro1 promoter in transgenic potato.

MAIN CONCLUSION: The PmBiPPro1 promoter of the luminal binding protein (BiP) from Douglas-fir is fully functional in transgenic potato, responsive to wounding, and has high transcriptional activity in tubers. A predefined pattern and level of transgene expression targeted to specific tissues or organs and at a particular developmental stage is a pre-requisite for the successful development of plants with desired traits. Here, we evaluated the transcriptional activity of the PmBiPPro1 promoter of the luminal binding protein (BiP) from Douglas-fir, by expressing reporter ß-D-glucuronidase (GUS) gene constructs containing three different PmBiPPro1 promoter versions (2258 bp, 1259 bp, and 278 bp) in transgenic potato. In conifers, this promoter regulates the endoplasmic reticulum (ER) molecular chaperon of the HSP70 stress-related protein family and is essential for proper functioning of the ER. Stable expression analysis demonstrated that two of three PmBiPPro1 promoter versions (PmBiPPro1-1 and PmBiPPro1-3) were fully functional in the heterologous host, exhibited high transcriptional activities in the leaves of unstressed potatoes, and were responsive to wounding. Deletion analysis showed that the positive cis-active regulatory elements necessary for higher level expression resided within the - 1243 to - 261 region, whereas negative cis-active elements encompassed nucleotides - 2242 to - 1243. Histochemical staining revealed high level of GUS activities in tissues associated with a high rate of cell division and secretory activities. Most importantly, the PmBiPPro1 promoters, especially the full-length version, had activity in microtubers at a level that was much higher than in any other potato organ or tissue. The - 2242 to - 1243 bp region likely contains important cis element(s) that interact with tuber-specific transcription factors required for promoter activation in the storage organs. The organ-specific activity of the PmBiPPro1 promoters may be useful for targeted expression of heterologous molecules in potato tubers.

Chirality Inversion on the Carbon Dot Surface via Covalent Surface Conjugation of Cyclic α-Amino Acid Capping Agents.

Manipulating the chiroptical properties at the nanoscale is of great importance in stereoselective reactions, enantioseparation, self-assembly, and biological phenomena. In recent years, carbon dots have garnered great attention because of their favorable properties such as tunable fluorescence, high biocompatibility, and facile, scalable synthetic procedures. Herein, we report for the first time the unusual behavior of cyclic amino acids on the surface of carbon dots prepared via microwave-based carbonization. Various amino acids were introduced on the surface of carbon dots via EDC/NHS conjugation at room temperature. Circular dichroism results revealed that although most of the surface conjugated amino acids can preserve their chirality on negatively charged, "bare" carbon dots, the "handedness" of cyclic α-amino acids can be flipped when covalently attached on carbon dots. Moreover, these chiroptical carbon dots were found to interact with the cellular membrane or its mimic in a highly selective manner due to their acquired asymmetric selectivity. A comprehensive inhibitor study was conducted to investigate the pathway of cellular trafficking of these carbon dots. Overall, it was concluded that the chirality of the amino acid on the surface of carbon dots could regulate many of the cellular processes.

Nano-Assembly of Pamitoyl-Bioconjugated Coenzyme-A for Combinatorial Chemo-Biologics in Transcriptional Therapy.

Pathogenesis, the biological mechanism that leads to the diseased state, of many cancers is driven by interruptions to the role of Myc oncoprotein, a regulator protein that codes for a transcription factor. One of the most significant biological interruptions to Myc protein is noted as its dimerization with Max protein, another important factor of family of transcription factors. Binding of this heterodimer to E-Boxes, enhancer boxes as DNA response element found in some eukaryotes that act as a protein-binding site and have been found to regulate gene expression, are interrupted to regulate cancer pathogenesis. The systemic effectiveness of potent small molecule inhibitors of Myc-Max dimerization has been limited by poor bioavailability, rapid metabolism, and inadequate target site penetration. The potential of gene therapy for targeting Myc can be fully realized by successful synthesis of a smart cargo. We developed a "nuclein" type nanoparticle "siNozyme" (45 ± 5 nm) from nanoassembly of pamitoyl-bioconjugated acetyl coenzyme-A for stable incorporation of chemotherapeutics and biologics to achieve remarkable growth inhibition of human melanoma. Results indicated that targeting transcriptional gene cMyc with siRNA with codelivery of a topoisomerase inhibitor, amonafide caused ∼90% growth inhibition and 95% protein inhibition.

Revisiting Polyarenes and Related Molecules: An Update of Synthetic Approaches and Structure-Activity-Mechanistic Correlation for Carcinogenesis.

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.

Macromolecularly "Caged" Carbon Nanoparticles for Intracellular Trafficking via Switchable Photoluminescence.

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.

Paper-Based Analytical Biosensor Chip Designed from Graphene-Nanoplatelet-Amphiphilic-diblock-co-Polymer Composite for Cortisol Detection in Human Saliva.

Cortisol has been identified as a biomarker in saliva to monitor psychological stress. In this work, we report a label-free paper-based electrical biosensor chip to quantify salivary cortisol at a point-of-care (POC) level. A high specificity of the sensor chip to detect cortisol with a detection limit of 3 pg/mL was achieved by conjugating anticortisol antibody (anti-CAB) on top of gold (Au) microelectrodes using 3,3'-dithiodipropionic acid di(N-hydroxysuccinimide ester (DTSP) as a self-assembled monolayer (SAM) agent. The electrode design utilized poly(styrene)-block-poly(acrylic acid) (PS67-b-PAA27) polymer and graphene nanoplatelets (GP) suspension coated on filter paper to increase the sensitivity of the immune response. A biosensor chip was then integrated with a lab-built low-cost miniaturized printed circuit board (PCB) to provide an electrical connection and to wirelessly transmit/receive electrical signals using MATLAB. This fully integrated proposed hand-held device successfully exhibited a wide cortisol-detection range from 3 pg/mL to 10 µg/mL, with a sensitivity of 50 Ω (pg mL-1)-1. The performance of the proposed cortisol sensor chip was validated using an enzyme-linked immunosorbent assay (ELISA) technique with a regression value of 0.9951. The advantages of the newly developed cortisol immune biosensor over previously reported chips include an improved limit of detection, no need for additional redox medium for electron exchange, faster response to achieve stable data, excellent shelf life, and its economical production.

Genomic DNA Interactions Mechanize Peptidotoxin-Mediated Anticancer Nanotherapy.

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.

Defined Host-Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer.

Signal transducer and activator of transcription factor 3 (STAT-3) is known to be overexpressed in cancer stem cells. Poor solubility and variable drug absorption are linked to low bioavailability and decreased efficacy. Many of the drugs regulating STAT-3 expression lack aqueous solubility; hence hindering efficient bioavailability. A theranostics nanoplatform based on luminescent carbon particles decorated with cucurbit[6]uril is introduced for enhancing the solubility of niclosamide, a STAT-3 inhibitor. The host-guest chemistry between cucurbit[6]uril and niclosamide makes the delivery of the hydrophobic drug feasible while carbon nanoparticles enhance cellular internalization. Extensive physicochemical characterizations confirm successful synthesis. Subsequently, the host-guest chemistry of niclosamide and cucurbit[6]uril is studied experimentally and computationally. In vitro assessments in human breast cancer cells indicate approximately twofold enhancement in IC50 of drug. Fourier transform infrared and fluorescence imaging demonstrate efficient cellular internalization. Furthermore, the catalytic biodegradation of the nanoplatforms occur upon exposure to human myeloperoxidase in short time. In vivo studies on athymic mice with MCF-7 xenograft indicate the size of tumor in the treatment group is half of the controls after 40 d. Immunohistochemistry corroborates the downregulation of STAT-3 phosphorylation. Overall, the host-guest chemistry on nanocarbon acts as a novel arsenal for STAT-3 inhibition.

Carotenoid Nanovector for Efficient Therapeutic Gene Knockdown of Transcription Factor FOXC1 in Liver Cancer.

Transcription factor FOXC1 has been implicated to play a critical role in hepatocellular carcinoma (HCC) progression, but targeting FOXC1 for therapeutic benefit remains a challenge owing to its location inside the cell nucleus. Herein we report successful therapeutic gene knockdown of transcription factor FOXC1 in liver cancer cells through efficient delivery of siFOXC1 using novel carotenoid functionalized dendritic nanoparticles (CDN). This delivery system also displayed a markedly reduced toxicity profile compared to a standard siRNA transfection agent. We were able to achieve ∼90% FOXC1 knockdown using the CDN-siFOXC1 complex. Additionally, it was found to have ∼18% greater delivery efficiency compared to treatments with particles which have no carotenoid tagging, thereby emphasizing the role of carotenoid mediated cell internalization in the efficient delivery of CDN-siFOXC1 complex in liver cancer cells.

Tunable Luminescent Carbon Nanospheres with Well-Defined Nanoscale Chemistry for Synchronized Imaging and Therapy.

In this work, we demonstrate the significance of defined surface chemistry in synthesizing luminescent carbon nanomaterials (LCN) with the capability to perform dual functions (i.e., diagnostic imaging and therapy). The surface chemistry of LCN has been tailored to achieve two different varieties: one that has a thermoresponsive polymer and aids in the controlled delivery of drugs, and the other that has fluorescence emission both in the visible and near-infrared (NIR) region and can be explored for advanced diagnostic modes. Although these particles are synthesized using simple, yet scalable hydrothermal methods, they exhibit remarkable stability, photoluminescence and biocompatibility. The photoluminescence properties of these materials are tunable through careful choice of surface-passivating agents and can be exploited for both visible and NIR imaging. Here the synthetic strategy demonstrates the possibility to incorporate a potent antimetastatic agent for inhibiting melanomas in vitro. Since both particles are Raman active, their dispersion on skin surface is reported with Raman imaging and utilizing photoluminescence, their depth penetration is analysed using fluorescence 3D imaging. Our results indicate a new generation of tunable carbon-based probes for diagnosis, therapy or both.

Next generation carbon nanoparticles for efficient gene therapy.

In a pursuit to develop a commercially exploitable and traceable gene delivery vehicle, here, we develop next generation carbon nanoparticle-DNA complex (CNPLex). CNPLexes were used to transfect green fluorescent protein (GFP) reporter gene containing plasmid DNA (pDNA) pEGFP-N1 targeting breast cancer cells MCF-7 and MDA-MB231. Prepared CNPs were optimized for particle size, surface potential, polymer surface decoration, absorbance efficiency, fluorescence efficiency, IR spectroscopic signatures, and DNA loading and release efficiencies. Rigorous biophysical methods were employed to determine the variations in physicochemical properties of CNPs after surface decoration with polymers followed by complexation with pDNA. Optimized CNPLexes were used to deliver pEGFP-N1 plasmid and efficiency of GFP was followed by fluorescence microscopy and quantified by flow assisted cell sorting. Lipofectamine2000 was used as positive control according to manufacturer's protocol and found to be comparative in transfection efficiency with one of our novel formulations. Further evaluation of cell toxicity and cell viability was performed by LDH activity and MTT assay, respectively. It was found that cell toxicity furnished by polymer decorated carbon nanoparticles was significantly low compared to the parent polymer (polyethylenimine, PEI). Similarly cell viability was found to be much higher with CNPLexes compared to PEI alone. This established the developed particles as better transfecting agents for reporter gene plasmid pEGFP-N1 compared to PEI and showed similar efficacy to one of the best known commercial transfection agents Liofectamine2000 in breast cancer cells MCF-7 and MDA-MB231.

Nanoscopic poly-DNA-cleaver for breast cancer regression with induced oxidative damage.

A novel strategy for efficient "nanodelivery" of DNA-cleaving molecules for breast cancer regression is presented here. The synthetic methodology can be tweaked for controlled delivery and better bioavailability of effective doses of these DNA-cleaving agents through a defined self-assembled polymeric nanoarchitecture. In vitro studies in ER+ and ER- breast cancer human cell lines confirmed an efficient "nano"-delivery of DNA-cleaving molecules and indicated their capability to mediate oxidative damage to nucleobases and/or to the 2-deoxyribose moiety. Prepared E-poly-DNA-cleaver and C-poly-DNA-cleaver were found to be interacting with plasmid DNA pBR322 (pDNA) and active to cause oxidative cleavage of pDNA in the presence of ascorbic acid and H2O2. They were found to be significantly active as DNA cleaving agents in vitro and showed highly improved cancer regression in MCF-7 and MD-MB231 cancer cells compared to small molecule DNA cleaver. Surface conjugated nanoparticles were found to be more effective than noncovalent encapsulation and the small molecule agent, whereas in all the cases RCM was significantly inactive toward DNA cleavage. Blood contact complement activation properties were evaluated to gauge their likelihood to promote acute toxicity following systemic administration. The complement activation analyses together with the blood smear study confirm the feasibility of using these poly-DNA-cleavers without risk of induced immune response.

In situ carbonization metamorphoses porous silica particles into biodegradable therapeutic carriers of lesser consequence on TGF-ß1 mediated fibrosis.

Extensive modifications have been made to the synthesis protocol for porous silica particles to improve the shape, size and yield percentage, but problems associated with improvement in biodegradability and decrease in chances to induce side effects still remain a concern. To circumvent these limitations, a facile modification strategy has been employed through in situ carbonization of porous silica particles. Herein, carbon particles were integrated within porous silica core-shell particles (Si-P-CNPs) during the synthesis process and found to preserve the ordered structural morphology. Curcumin was used as a model drug for loading in prepared Si-P-CNPs whereas lung cancer cells were used as a model system to study the in vitro fate. These Si-P-CNPs showed improved drug loading, drug effectivity, biodegradability and avoidance of interaction with transforming growth factor ß1 (TGF-ß1) indicating the possibility of reducing the chances of lung fibrosis and thereby enhancing the safety profile over conventional porous silica particles.

Pyridine-2,6-Dicarboxamide Proligands and their Cu(II)/Zn(II) Complexes Targeting Staphylococcus Aureus for the Attenuation of In Vivo Dental Biofilm.

In the pursuit to combat stubborn bacterial infections, particularly those stemming from gram-positive bacteria, this study is an attempt to craft a precision-driven platform characterized by unparalleled selectivity, specificity, and synergistic antimicrobial mechanisms. Leveraging remarkable potential of metalloantibiotics in antimicrobial applications, herein, this work rationally designs, synthesizes, and characterizes a new library of Pyridine-2,6-dicarboxamide ligands and their corresponding transition metal Cu(II)/Zn(II) complexes. The lead compound L11 demonstrates robust antibacterial properties against Staphylococcus aureus (Minimum Inhibitory Concentration (MIC) = 2-16 µg mL-1), methicillin and vancomycin-resistant S. aureus (MIC = 2-4 µg mL-1) and exhibit superior antibacterial activity when compared to FDA-approved vancomycin, the drug of last resort. Additionally, the compound exhibits notable antimicrobial efficacy against resistant enterococcus strains (MIC = 2-8 µg mL-1). To unravel mechanistic profile, advanced imaging techniques including SEM and AFM are harnessed, collectively suggesting a mechanistic pathway involving cell wall disruption. Live/dead fluorescence studies further confirm efficacy of L11 and its complexes against S. aureus membranes. This translational exploration extends to a rat model, indicating promising in vivo therapeutic potential. Thus, this comprehensive research initiative has capabilities to transcends the confines of this laboratory, heralding a pivotal step toward combatting antibiotic-resistant pathogens and advancing the frontiers of metalloantibiotics-based therapy with a profound clinical implication.