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. © 2020 American Chemical Society.

Bimlesh Lochab

Chemistry

(SoNS) School of Natural Sciences

Yadav N.

Kannan D.

Patil S.

Singh S.

<p>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.</p>

Shiv Nadar University

ACS Applied Bio Materials

Graphene oxide (GO) is an attractive precursor for graphene, provided by the well-known wet-chemical oxidative process. The intercalation of acid in graphite is considered as a crucial step, and its subsequent oxidation holds special relevance in synthesis. So far, the above chemistry is dominated by usage of H2SO4. Recently, H3PO4 appeared as a suitable intercalant for graphite. However, its role is not well understood in the formation of GO, especially when present as a co-acid with H2SO4. Additionally, a relatively lower toxicity of H3PO4 as compared to H2SO4, elimination of toxic NaNO3 usage, and a facile purification protocol are encouraging in terms of low-cost production of GO with a reduced environmental impact. Here, we report the systematic synthesis and characterization of GOs prepared with the variation in the ratio of H2SO4 and H3PO4. Ab initio simulations revealed that intercalation is primarily affected because of the usage of a mixture of co-acids. Interestingly, the ratio of the acids dictated the nature of the functionalities, extent of the defects, and morphology of the GOs, accounting for a pronounced effect on thermal stability, contact angle, zeta potential, and hydrodynamic size. The oxidation mechanism showed a predominance of H2SO4 content, whereas H3PO4 is found to mainly govern the intercalation of graphite, thereby affecting the acid-based intercalation-oxidation chemistry of graphite. The as-prepared GO suspension exhibited a high adsorption capacity for methylene blue dye removal in water, suggesting its potential as an adsorbent material in water treatment. The utility of the two acids affects the acid-based intercalation-oxidation chemistry of graphite and simultaneously may open up new opportunities for synthesized GOs, on tenets of green chemistry, in a wide arena of applications. © 2019 American Chemical Society.

Fulltext

ACS Omega

Control of Functionalities in GO: Effect of Bronsted Acids as Supported by Ab Initio Simulations and Experiments

Among 2-D nanostructures, graphene oxide is considered as the most attractive precursor nanomaterial for the utility of graphene in a variety of applications. There are problems associated with its mass production, which demands development of better and easier synthetic protocols. In addition, a chemical approach with a better control over degree of oxidation and nature of functionalities is simultaneously crucial for designing their structural modifications and the corresponding applications. Herein, three types of GOs are prepared by Hummers’, Intermediate and Improved method. A primary reaction step in GO synthesis is the formation of graphite intercalation compounds (GICs). The efficiency of oxidation and intercalant efficiency, non-oxidative Bronsted acid H 3 PO 4 /H 2 SO 4 and H 2 SO 4 are studied and properties are compared with the classical intercalant, H 2 SO 4 /NaNO 3 . A modulation in degree and nature of oxidative defects, flake size and stability of aqueous dispersion is observed, as supported by various analytical techniques. Depending upon the reaction conditions, the synthesized GOs revealed predominance of different type of oxidative functionalities and thereby reflected in associated physical properties, which is helpful to guide their usage for specific applications. © 2019 Elsevier B.V.

FlatChem

A comparative study of graphene oxide: Hummers, intermediate and improved method

Conjugates of poly(amidoamine) (PAMAM) with modified graphene oxide (GO) are attractive nonviral vectors for gene-based cancer therapeutics. GO protects siRNA from enzymatic cleavage and showed reasonable transfection efficiency along with simultaneous benefits of low cost and large scale production. PAMAM is highly effective in siRNA delivery but suffers from high toxicity with poor in vivo efficacy. Co-reaction of GO and PAMAM led to aggregation and more importantly, have detrimental effect on stability of dispersion at physiological pH preventing their exploration at clinical level. In the current work, we have designed, synthesized, characterized and explored a new type of hybrid vector (GPD), using GO synthesized via improved method which was covalently tethered with poly(ethylene glycol) (PEG) and PAMAM. The existence of covalent linkage, relative structural changes and properties of GPD is well supported by Fourier transform infrared (FTIR), UV-visible (UV-vis), Raman, X-ray photoelectron (XPS), elemental analysis, powder X-ray diffraction (XRD), thermogravimetry analysis (TGA), dynamic light scattering (DLS), and zeta potential. Scanning electron microscopy (SEM), and transmission electron microscopy (TEM) of GPD showed longitudinally aligned columnar self-assembled ∼10 nm thick polymeric nanoarchitectures onto the GO surface accounting to an average size reduction to ∼20 nm. GPD revealed an outstanding stability in both phosphate buffer saline (PBS) and serum containing cell medium. The binding efficiency of EPAC1 siRNA to GPD was supported by gel retardation assay, DLS, zeta potential and photoluminescence (PL) studies. A lower cytotoxicity with enhanced cellular uptake and homogeneous intracellular distribution of GPD/siRNA complex is confirmed by imaging studies. GPD exhibited a higher transfection efficiency with remarkable inhibition of cell migration and lower invasion than PAMAM and Lipofectamine 2000 suggesting its role in prevention of breast cancer progression and metastasis. A significant reduction in the expression of the specific protein against which siRNA was delivered is revealed by Western blot assay. Furthermore, a pH-triggered release of siRNA from the GPD/siRNA complex was studied to provide a mechanistic insight toward unloading of siRNA from the vector. Current strategy is a way forward for designing effective therapeutic vectors for gene-based antitumor therapy. © 2018 American Chemical Society.

ACS Applied Materials and Interfaces

Stable Dispersions of Covalently Tethered Polymer Improved Graphene Oxide Nanoconjugates as an Effective Vector for siRNA Delivery

In this work, we report the synthesis of hydrophilic and surface-functionalized superparamagnetic iron oxide nanoparticles (SPIOs) to utilize them as nanomedicines for treating liver cancer via magnetic fluid hyperthermia (MFH)-based thermotherapy. For this purpose, initially, we have synthesized the SPIOs through co-precipitation/thermolysis methods, followed by in situ surface functionalization with short-chained molecules, such as 1,4-diaminobenzene (14DAB), 4-aminobenzoic acid (4ABA) and 3,4-diaminobenzoic acid (34DABA) and their combination with terephthalic acid (TA)/2-aminoterephthalic acid (ATA)/trimesic acid (TMA)/pyromellitic acid (PMA) molecules. The as-prepared SPIOs are investigated for their structure, morphology, water dispersibility, and magnetic properties. The heating efficacies of the SPIOs are studied in calorimetric MFH (C-MFH) with respect to their concentrations, surface coatings, dispersion medium, and applied alternating magnetic fields (AMFs). Although all of the as-prepared SPIOs have exhibited superparamagnetic behavior, only 14DAB-, 4ABA-, 34DABA-, and 4ABA-TA-coated SPIOs have shown higher magnetization values (Ms = 55-71 emu g-1) and good water dispersibility. In C-MFH studies, 34DABA-coated SPIO-based aqueous ferrofluid (AFF) has revealed faster thermal response to the applied AMF and reached therapeutic temperature even at the lowest concentration (0.5 mg mL-1) compared with 14DAB-, 4ABA-, and 4ABA-TA-coated SPIO-based AFFs. Moreover, 34DABA-coated SPIO-based AFF has exhibited high heating efficacies (i.e., specific absorption rate/intrinsic loss power values of 432.1 W gFe-1/5.2 nHm2 kg-1 at 0.5 mg mL-1), which could be mainly due to (i) enhanced π-π conjugation paths of surface-attached 34DABA coating molecules because of intrafunctional group attractions and (ii) improved anisotropy from the formation of clusters/linear chains of the SPIOs in ferrofluid suspensions, owing to interfunctional group attractions/interparticle interactions. Moreover, the 34DABA-coated SPIOs have demonstrated (i) very good cytocompatibility for 24/48 h incubation periods and (ii) higher killing efficiency of 61-88\% (via MFH) in HepG2 liver cancer cells as compared to their treatment with only AMF/water-bath-based thermotherapy. In summary, the 34DABA-coated SPIOs are very promising heat-inducing agents for MFH-based thermotherapy and thus could be used as effective nanomedicines for cancer treatments. © 2018 American Chemical Society.