Chemistry

Shiv Nadar University is a comprehensive, multidisciplinary, research-focused, and student-centric University offering a full range of academic programs at the undergraduate, postgraduate and doctoral level. With state-of-the-art infrastructure, the University comprises of academic wings, sophisticated labs, international standard sports facilities, amphitheaters, auditorium, conference rooms and smart classrooms. The University&rsquo;s goal is to become internationally recognized for the quality of its research and creative endeavors and their applicability to improving quality of life, generating new insights and expanding the boundaries of human knowledge creativity. Committed to excellence in teaching, research and service, the University aims to serve the higher education needs of India and the world beyond.

Shiv Nadar University

Herb-based extracellular vesicles (EV), inherently replete with bioactive proteins, RNA, lipids, and other medicinal compounds, are noncytotoxic and uniquely capable of cellular delivery to meet the ever-stringent challenges of ongoing clinical applications. EVs are abundant in nature, affordable, and scalable, but they are also incredibly fragile and stuffed with many biomolecules. To address the low drug binding abilities and poor stability of EVs, we demonstrated herb-based EVs (isolated from neem, mint, and curry leaves) conjugated with chitosan (CS) and PEGylated graphene oxide (GP) that led to their transformation into robust and efficient vectors. The designed conjugates successfully delivered estrogen receptor α (ERα1)-targeting siRNA to breast cancer MCF7 cells. Our data revealed that neem-based EV-CS-GP conjugates were most efficient in cellular siRNA delivery, which could be attributed to hyaluronic acid-mediated recognition of neem EVs by MCF7 cells via CD44 receptors. Our approach shows a futuristic direction in designing clinically viable, sustainable, nontoxic EV-based vehicles that can deliver a variety of functional siRNA cargos.

(SoNS) School of Natural Sciences

ACS Applied Bio Materials

Herb Extracellular Vesicle-Chitosan-PEGylated Graphene Oxide Conjugate Delivers Estrogen Receptor α Targeting siRNA to Breast Cancer Cells

The promise of artesunate’s (ART) role in anticancer properties steers a focus on drug repurposing. Potential nanocargo heterostructures, with each component having a specific role, are required for effective drug delivery. Here, we have developed a nanoformulation based on nanodiamonds studded with iron oxide that exhibits exceptional biocompatibility and effective cellular delivery of ART. The current drug delivery formulation has proven improved efficiency of the drug in generating higher reactive oxygen species (ROS), resulting in DNA damage and subsequent cellular apoptosis.

ACS Materials Letters

Multifunctional Multicomponent Highly Biocompatible pH-Responsive Iron-Oxide Embedded Nanodiamond Cargo for Artesunate to Inhibit Cancer Growth

Glioblastoma multiforme (GBM) is known as the primary malignant and most devastating form of tumor found in the central nervous system of the adult population. The active pharmaceutical component in current chemotherapy regimens is mostly hydrophobic and poorly water-soluble, which hampers clinical implications. Nanodrug formulations using nanocarriers loaded with such drugs assisted in water dispersibility, improved cellular permeability, and drug efficacy at a low dose, thus adding to the overall practical value. Here, we successfully developed a water-dispersible and biocompatible nanocargo (GO-PEG) based on covalently modified graphene oxide (GO) with a 6-armed poly(ethylene glycol) amine dendrimer for effective loading of the two hydrophobic anticancer drug molecules, CPI444 and vatalanib. These drug molecules target adenosine receptor&nbsp;(A2AR), vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and type III stem cell receptor tyrosine kinase (c-KIT), which plays a crucial role in cancers. The effective cellular delivery of the drugs when loaded on GO-PEG is attributed to the increased permeability of the drug-nanoconjugate formulation. We observed that this combinatorial drug treatment with nanocargo resulted in a significant reduction in the overall cell survival as supported by reduced calcium levels and stem cell markers such as Oct4 and Nanog, which are two of the prime factors for GBM stem cell proliferation. Furthermore, reduced expression of CD24 upon treatment with nanoformulation impeded cellular migration. Cellular assays confirmed inhibition of cell proliferation, migration, and angiogenic potential of GBM treated with GO-PEG–Drug conjugates. Ultimately, GBM U87 cells assumed programmed cell death at a very low concentration due to nanocarrier-mediated drug delivery along with the chosen combination of drugs. Together, this study demonstrated the advantage of GO-PEG mediated combined delivery of CPI444 and vatalanib drugs with increased permeability, a three-pronged combinatorial strategy toward effective GBM treatment.

Frontiers in Oncology

Combinatorial therapy of CPI444 and Vatalanib loaded on PEGylated graphene oxide: Effective nanoformulation to target glioblastoma multiforme

Nanodiamonds (NDs) are increasingly being assessed as potential candidates for drug delivery in cancer cells and they hold great promise in overcoming the side effects of traditional chemotherapeutics. In the current work, carboxylic acid functionalized nanodiamonds (ND-COOH) were covalently modified with poly(amidoamine) dendrimer (PAMAM) to form amine-terminated nanodiamonds (NP). Unlike ND-COOH, the chemically modified nanodiamond platform NP revealed a pH-independent aqueous dispersion stability, enhancing its potential as an effective carrier. Physical encapsulation of poorly water soluble cabazitaxel (CTX) drug on NP formed ND-PAMAM-CTX (NPC) nanoconjugates and substantially reduced the size of CTX from micrometer to nanometer. CTX was localized within the pores of nanoparticle aggregates and the cavities of the PAMAM dendrimer, thus facilitating the loaded drug’s controlled and sustained release. NPC’s cumulative CTX release efficiency was determined to be ∼95% at pH 4 after 96 h. A high cellular uptake of NPC both within the cytoplasm and nucleus of U87 cells is confirmed, accounting for a reduced IC50 value (1 nM). Both the cell cycle and Western blot analyses confirmed enhanced cell death and suppressed tubulin protein expression in NPC-treated cells. A significantly high inhibition to cell division with early apoptosis and reduced metastasis demonstrates the effective loading of CTX dosages on the nanocarrier. The present work highlights the potential of a newly designed nanocarrier NP as an efficient nanocargo for cellular delivery applications and may provide future insights to treat one of the most aggressive tumors in neuro-oncological research, glioblastoma multiforme (GBM).

Dendrimer functionalized nanodiamonds as safe and efficient drug carrier for cancer therapy: Nucleus penetrating nanoparticles

Resistance to antimicrobial agents in Gram-positive bacteria has become a major concern in the last decade. Recently, nanoparticles (NP) have emerged as a potential solution to antibiotic resistance. We synthesized three reduced graphene oxide (rGO) nanoparticles, namely rGO, rGO-S, and rGO-S/Se, and characterized them using X-ray diffraction (PXRD), Raman analysis, and thermo-gravimetric analysis. Transmission electron microscopy confirmed spherical shape nanometer size S and S/Se NPs on the rGO surface. Antibacterial properties of all three nanomaterials were probed against Gram-positive pathogens Staphylococcus aureus and Enterococcus faecalis, using turbidometeric and CFU assays. Among the synthesized nanomaterials, rGO-S/Se exhibited relatively strong an-tibacterial activity against both Gram-positive microorganism tested in a concentration dependent manner (growth inhibition &gt;90% at 200 µg/mL). Atomic force microscopy of rGO-S/Se treated cells displayed morphological aberrations. Our studies also revealed that rGO composite NPs are able to deposit on the bacterial cell surface, resulting in membrane perturbation and oxidative stress. Taken together, our results suggest a possible three-pronged approach of bacterial cytotoxicity by these graphene-based materials. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

World University root node

Fulltext

Nanomaterials

Synthesis and Characterization of Sulfur and Sulfur-Selenium Nanoparticles Loaded on Reduced Graphene Oxide and Their Antibacterial Activity against Gram-Positive Pathogens

Polymorphism in drugs and bioactive molecules is not uncommon, and it has remained as one of the critical issues in drug development processes. While improving physicochemical properties of bioactive molecules has been a prime focus of the pharmaceutical chemists, not much efforts have been put toward the improvement of their potency via polymorphic modifications. Here, we consider five cases of 5-arylidene-2-aminothiazolidinones derivatives, the known anticancer agents, and discover eights polymorphs in three out of the five cases. We perform systematic crystallization experiments and detailed crystal structure analysis of the eight polymorphs and two compounds, estimate both their energetic and thermal stabilities, and compare their solid state properties. We also compare in-solution properties, e.g., equilibrium solubility, intrinsic dissolution rate, and phase stability, of three polymorphs of one of the cases. Further, we study the extent of inhibition imposed by those eight polymorphs and seven bulk and crystal forms of the compounds on the proliferation of MCF7 breast cancer cells and also the extent of their binding to the isozyme γ-enolase. Furthermore, we perform MD simulations on the eight polymorphs and one compound to estimate and compare their binding affinity with γ-enolase. Our experimental and MD simulation analyses in general emphasize the importance of polymorphism in improving the biological potency of individual molecules. © 2022 American Chemical Society. All rights reserved.

Molecular Pharmaceutics

Tuning Potency of Bioactive Molecules via Polymorphic Modifications: A Case Study

Solid-state rechargeable zinc-Air batteries (ZABs) are gaining interest as a class of portable clean energy technology due to their advantages such as high theoretical energy density, intrinsic safety, and low cost. It is expected that an appropriately triple-phase boundary (TPB) engineered, bifunctional oxygen reaction (OER and ORR) electrocatalyst at the air-electrode of ZABs can redefine the performance characteristics of these systems. To explore this possibility, an electrode material consisting of manganese-cobalt-based bimetallic spinel oxide (MnCo2O4)-supported nitrogen-doped entangled graphene (MnCo2O4/NEGF) with multiple active sites responsible for facilitating both OER and ORR has been prepared. The porous 3D graphitic support significantly affects the bifunctional oxygen reaction kinetics and helps the system display a remarkable catalytic performance. The air electrode consisting of the MnCo2O4/NEGF catalyst coated over the gas diffusion layer (GDL) ensures the effective TPB, and this feature works in favor of the rechargeable ZAB system under the charging and discharging modes. As an important structural and functional attribute of the electrocatalyst, the porosity and nitrogen doping in the 3D conducting support play a decisive aspect in controlling the surface wettability (hydrophilicity/hydrophobicity) of the air electrode. The fabricated solid-state rechargeable ZAB device with the developed electrode displayed a maximum peak power density of 202 mW cm-2, which is significantly improved as compared to the one based on the Pt/C + RuO2standard catalyst pair (124 mW cm-2). The solid-state device which displayed an initial charge-discharge voltage gap of only 0.7 V at 10 mA cm-2showed only a small increment of 86 mV after 50 h. © 2022 American Chemical Society. All rights reserved.

ACS Applied Energy Materials

Air-Cathode Interface-Engineered Electrocatalyst for Solid-State Rechargeable Zinc-Air Batteries

A large number of people are suffering globally from diabetes due to metabolic disorders characterized by abnormally high blood sugar (glucose), which inflicts severe health issues as well as huge economic burdens. In this study, we have reported an efficient and eco-friendly biosynthesis of hydrophilic zinc oxide nanoparticles (ZnO NPs, labeled as PC1 and C1) for antidiabetic treatment using an aqueous extract of Plumeria obtusa and Tabernaemontana divaricata flowers, respectively. Phase purity, structure, morphology, and dispersibility of the as-synthesized PC1/C1 have been characterized by various analytical techniques such as UV–visible spectroscopy (UV–vis), Powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and dynamic light scattering (DLS). The UV–vis spectrum of the PC1/C1 showed maximum absorbance at ~ 370 nm and the PXRD pattern confirmed their hexagonal wurtzite crystalline structure. Besides, SEM displayed sheet and honeycomb-like shape of the PC1 and C1 while FTIR and TGA revealed the attached surface coatings of the PC1/C1. DLS results showed narrow size distribution of the PC1 and C1 in the range of 150–156 and 315–400 nm, respectively. Moreover, the zeta potential values of the as-prepared PC1 and C1 are determined as -47 and -57 mV indicating their good colloidal stability in an aqueous suspension. In vitro study has been performed to show the α-amylase inhibition activity. Furthermore, the PC1/C1 are investigated for their antidiabetic efficacy in streptozotocin (STZ)-induced diabetes in the C57BL/6 male mice. Both the PC1/C1 displayed a significant antidiabetic potential; however, the blood glucose level has been significantly reduced (p &lt; 0.05) in the STZ-induced diabetic mice treated with PC1 as compared to the C1. Overall, PC1 and C1 are found to be very promising antidiabetic candidates for the in vivo antidiabetic treatment. Graphical abstract: [Figure not available: see fulltext.]. © 2022, Institute of Chemistry, Slovak Academy of Sciences.

Chemical Papers

Biosynthesis of hydrophilic zinc oxide nanoparticles using Plumeria obtusa and Tabernaemontana divaricata flower extract for antidiabetic treatment

The latest fourth-generation oxazine-ring substituted thiophene-based benzoxazine monomers and polymers with variation in the degree of phenyl substitution (with and without) in the oxazine-ring were synthesized and characterized. Thiophene-based di-substituted benzoxazine undergoes ring-opening polymerization at a low temperature with a minimal mass loss during polymerization as supported by molecular geometry-guided intramolecular interactions. This class of monomers provides ample opportunities to design at the molecular level high-performance polybenzoxazines with promising smart applications. © 2022 The Royal Society of Chemistry.

Chemical Communications

Synthesis and thermal behaviour of thiophene-based oxazine-ring substituted benzoxazine monomers &amp; polymers

Nanoscale assembly of ultrasmall metal nanoclusters (MNCs) by means of molecular forces has proven to be a powerful strategy to engineer their molecule-like properties in multiscale dimensions. By leveraging depletion attraction as the guiding force, herein, we demonstrate the formation of kinetically trapped NCs assemblies with enhanced photoluminescence (PL) and excited state lifetimes and extend the principle to cluster impregnated cationic nanogels, nonluminescent Au(I)-thiolate complexes, and weakly luminescent CuNCs. We further demonstrate a thermal energy driven kinetic barrier breaking process to isolate these assemblies. These isolated assemblies are thermodynamically stable, built from a strong network among several discrete, ultrasmall AuNCs and exhibit several unusual properties such as high stability in various pH, strong PL, microsecond lifetimes, large Stocks shifts, and higher accumulation in the lysosome of cancer cells. We anticipate our strategy may find wider use in creating a large variety of MNC-based assemblies with many unforeseen arrangements, properties, and applications. © 2022 American Chemical Society.