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.

Chemistry

(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

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.

World University root node

Chemical Papers

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

A fully biobased benzoxazine monomer, V-fa (using <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/vanillin">vanillin</a> and furfurylamine) was grafted onto chitosan (CS) at different weight ratios (CXVY) using "grafting to" benign <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/schiff-base">Schiff base</a> chemistry. Incorporation of V-fa onto CS increased the tensile strength and improved chemical resistance of the CS-graft-V-fa films. Reversible labile linkages, expansion of CS galleries and leaching out of phenolic species from biobased <a href="https://www.sciencedirect.com/topics/materials-science/polymer-films">polymer films</a> led to an improved <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/antibacterial-activity">antibacterial activity</a> against Staphylococcus aureus, which is ∼125 times higher than the bare CS film, V-fa and oligomeric V-fa. The leached out species from films were analyzed extensively by NMR, FTIR, GPC, ABTS and HRMS analysis. Oxidative-stress seems to be responsible for <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/antibacterial-activity">antibacterial activity</a>. Current work illustrates an attractive synthetic approach and the improved antibacterial performance of biobased CS-graft-poly(V-fa) films which may hold as a potential alternative for wound-healing and implant applications in future.

Carbohydrate Polymers

Antibacterial performance of fully biobased chitosan-grafted-polybenzoxazine films: Elaboration and properties of released material

Development of drugs to tackle the ever-increasing cases of cancer and many other diseases including any pandemic is itself challenging. Repurposing existing drugs is an upcoming drug development strategy established for the reuse of existing licensed drugs to ensure accessible, sustainable, and affordable care against cancer. Herein, we presented a nanochemotherapeutic approach based on PEGylated graphene oxide (GO-PEG) loaded with superparamagnetic iron oxide nanoparticles (NPs) and a sustainable natural origin drug, artesunate (ART) to kill cancerous cells. GO-PEG provided a larger surface area to load the dual cargo, iron oxide NPs (∼40%) and ART (∼13%), at a high loading efficiency and simultaneously affected nanotization and crystallinity of the iron oxide NPs. The morphology and internalization of NPs were determined qualitatively and quantitatively by atomic force microscopy (AFM)–Raman imaging and atomic absorption spectroscopy (AAS) analysis, respectively. Furthermore, the loading and unloading of iron reserves were characterized by high-resolution transmission electron microscopy (TEM) images. The loaded iron oxide NPs underwent a pH-triggered release of iron ions, which is higher in acidic pH than in neutral pH. A ∼sevenfold reduction in the IC50 value of ART upon treatment with the designed nanoconjugate is observed. ART is repositioned as a therapeutic drug against cancer cells, and its efficacy is amplified by the Fenton reaction due to iron oxide NPs, as confirmed by a high oxidative stress generated within the cells. The current work suggests that ART and iron oxide NPs loaded on GO-PEG, a biocompatible carrier, are a promising drug–nanoparticle conjugate for cancer treatment.