Murugaraj Jeyaraj

Biogenic metal nanoformulations induce Bax/Bcl2 and caspase mediated mitochondrial dysfunction in human breast cancer cells (MCF 7)

Nanostructures of noble metals have been extensively studied recently because of their impressive physiochemical properties and wide range of applications in biology and medicine. In this study, the anticancer efficacy of green synthesized silver and gold nanoparticles (AgNPs and AuNPs) was assessed against human breast carcinoma cells (MCF-7). Treatment with different concentrations of NPs triggers the cellular toxicity in a dose and time dependent manner. Morphological features of apoptosis were measured using cell wall integrity, acridine orange/ethidium bromide and Hochest staining methods which clearly distinguishes the viable cells and the cells undergoing apoptosis. Flow cytometry and DNA fragmentation analysis were also used to substantiate that NPs induced cytotoxicity was primarily mediated by G2/M cell cycle arrest and apoptosis. NPs provoke intracellular reactive oxygen species that cause damage to various cellular components. Furthermore, the gene expression studies such as reverse transcription – polymerase chain reaction, quantitative polymerase chain reaction and western blot analysis shows the upregulation of Bax, Bcl2, caspases-6 and -9, PARP, p53 and downregulation of Bcl-2 depicts the induction of apoptosis upon exposure to NPs. The overall results clearly shows that green synthesized metal NPs can potentially inhibit the proliferation of MCF-7 cells and trigger apoptosis through Bax/Bcl2 and caspase–cascade mediated mitochondrial dysfunction. This research concludes that biogenic metal nano-drug formulations can be utilized for cancer chemotherapy.

Correction: Dietary flavone chrysin (5,7-dihydroxyflavone ChR) functionalized highly-stable metal nanoformulations for improved anticancer applications

Nanomaterials of noble metals with unique size, shape and composition receives much attention owing to their versatile functionality in personalized cancer nanomedicine. Chrysin (ChR), a natural anticancer bioflavonoid, emerged as a potential drug therapy for almost all types of cancer, however it has poor solubility and bioavailability. Herein, we report a new approach to formulate biofunctionalized metallic silver (ChR–AgNPs) and gold (ChR–AuNPs) nanoparticles using ChR as a direct bioreductant and capping agent. Size and dispersity of nanoparticles (NPs) were controlled through fixing different reaction conditions such as the temperature, pH, concentration of metal ion, stoichiometric proportion of the reaction mixture and incubation time based on their optical properties and SPR effect in UV-visible spectroscopy. The role of hydroxyl and carbonyl groups in functionalizing the metal ions with ChR was confirmed with Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis. It was also substantiated that the oxygen group from ChR donates electrons to metal ion and results in complexation; ionic Ag+ and Au3+ were reduced to Ag0 and Au0 nano-forms. The physiochemical state of obtained NPs was characterized through different exclusive instrumentation, which shows the presence of highly-stable, spherical, crystalline ChR–AgNPs and ChR–AuNPs with an average size of 14 ± 6 nm and 6 ± 2 nm respectively. In vitro anticancer results revealed that the formulated metallic NPs exhibit enhanced cytotoxicity over ChR in the treatment of two different breast carcinoma cell lines (MDA-MB-231 and MDA-MB-468). Furthermore, it was evident that the NPs cause cell death via the induction of apoptosis. A hemolysis assay with human erythrocytes demonstrates good blood biocompatibility of the NPs. Thus, the ChR functionalized metal NPs can be potentially employed as a combinational drug-nano platform for breast cancer therapy.

Surface functionalization of natural lignin isolated from Aloe barbadensis Miller biomass by atom transfer radical polymerization for enhanced anticancer efficacy

Lignin (LIG), one of the major natural polymers in the biomass is widely used for various industrial and biomedical applications, mainly in its modified form of grafted lignin. The present study focuses on the isolation of lignin from Aloe barbadensis Miller by a microwave extraction technique and its applicability as a medicinal biomass. The isolated lignin was used for the synthesis of a drug carrier by grafting with methacrylate (MA). Lignin grafted methacrylate was synthesised (LIG-g-MA) via atom transfer radical polymerization (ATRP). 5-Fluorouracil (5-FU) was used as a model cancer drug and it was encapsulated on the hollow nanocarrier by the emulsion/solvent evaporation technique. While NMR spectroscopy elucidates the structure of the isolated lignin, FT-IR and XRD techniques address the binding nature and crystalline character of 5-FU loaded carrier. The surface morphology of the isolated lignin, grafted lignin and drug-loaded carrier was confirmed with SEM and TEM techniques. The encapsulation efficiency and in vitro drug release were studied to determine the efficiency of the carrier. The cell viability and cytotoxicity effect of 5-FU loaded on LIG-g-MA and unloaded LIG-g-MA were performed against MCF-7 and VERO cell lines. In short, the modified natural lignin based on LIG-g-MA hollow-nanofibrous material has been shown to be a potentially useful biocompatible nanocarrier in chemotherapy for cancer treatment.

Green synthesis of magnetic Fe3O4 nanoparticles using Couroupita guianensis Aubl. fruit extract for their antibacterial and cytotoxicity activities

Abstract In the present study, a sustainable green chemistry approach was established to fabricate magnetic Fe3O4 nanoparticles (Fe3O4NPs) using the aqueous fruit extract of edible C. guianensis (CGFE). Synthesized NPs were further confirmed with different high-throughput characterization techniques such as UV–visible spectroscopy, FT-IR, XPS, DLS and zeta potential analysis. Additionally, XRD, AFM, HRTEM and SQUID VSM demonstrate the generation of crystalline CGFe3O4NPs with mean diameter of 17 ± 10 nm. Interestingly, CGFe3O4NPs exhibit a stupendous bactericidal action against different human pathogens which depicts its antimicrobial value. A significant dose-dependent cytotoxic effect of CGFe3O4NPs was noticed against treated human hepatocellular carcinoma cells (HepG2).

Magneto-chemotherapy for cervical cancer treatment with camptothecin loaded Fe3O4 functionalized β-cyclodextrin nanovehicle

We portray a novel way to deal with the synthesis of iron oxide magnetic nanoparticle incorporated β-cyclodextrin (β-CD) nanocarrier stabilized by ethylenediamine tetra acetic acid (EDTA), which obtained remarkable biocompatibility and biodegradability. The functionality, crystalline nature, morphology and thermal decomposition nature of Fe3O4, β-CD–EDTA–Fe3O4 and β-CD–EDTA–Fe3O4/CPT nanocarriers were confirmed by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The mechanistic action of camptothecin (CPT) on cancer cells was studies relying to incorporation with the topoisomerase (topo I) and DNA complex formation. This prevented DNA re-ligation, causing DNA damage which resulted in apoptosis in cervical cancer (HeLa) cells. We noticed a higher number of cells arrested in the G1 phase with a decreasing cell count in the S phase and the G2/M phase at a lower concentration of β-CD–EDTA–Fe3O4/CPT. Consequently, via conjugation with Fe magnetic nanoparticles (MNPs), the molecular recognition between β-CD and target the cancerous cells make this nanovehicle a promising candidate for the non-invasive treatment of HeLa cells.

Co-encapsulation of dual drug loaded in MLNPs: Implication on sustained drug release and effectively inducing apoptosis in oral carcinoma cells

Combinations of natural bee wax flavones chrysin with a chemo drug have been exhibiting high potential with reduced adverse effect. To extend the synergistic effect of chrysin and improve the MLNPs (Multi Layer Nanoparticles) performance in drug release, layer-by-layer of poly [di(sodium carboxyphenoxy)phosphazene] (PDCPP) and poly (diallyldimethyl ammonium chloride) (PDADMAC) deposited on the CaCO3 nanoparticles (CCNPs) surface. The results suggest spherical MLNPs of 237 nm are formed with high drug loading content with enhanced cellular uptake. Under acidic conditions, multi layer structure effectively controls burst release, providing sustained drug release for long period. The combined effect of chrysin and cisplatin improved the cytotoxic potential of MLNPs at 25 μg.mL-1 concentration. Angiogenesis inhibitor chrysin activates reactive oxygen species (ROS) production and eventually leads to mitochondrial dysfunction. Furthermore, significant decreases of buccal pouch carcinoma in hamster model. Dual drug loaded MLNPs achieves 92% regressions of tumor volume as compared to cisplatin alone loaded MLNPs. In addition, Histopathology studies demonstrated the biocompatible effect of MLNPs on vital organs. This work provides a simple method to formulate multiple drugs in single nanosystem with high therapeutic efficacy on oral cancer.

Assembling of multifunctional latex-based hybrid nanocarriers from Calotropis gigantea for sustained (doxorubicin) DOX releases

Natural rubber Latex (Lax) is a colloidal dispersion of polymer particles in liquid and shows good biodegradable, biocompatibility, and non-toxicity. Natural polymers are the most important materials used in food packaging, micro/nano-drug delivery, tissue engineering, agriculture, and coating. In the present study, natural compounds extracted from plant Lax were designed to function as drug carriers using various surfactants via emulation and solvent evaporation method. Calotropis gigantea belongs to the family Apocynaceae and has received considerable attention in modern medicine, ayurvedeic, siddha, and traditional medicine. Since, we were isolated biodegradable, non-toxic, and biocompatible materials as latex from Calotropis gigantea plant. The Lax was separated as per their solubility nature and it was designed as a carrier using surfactant namely; Sorbitanmonolaurate (Span-20), sodium lauryl sulfate (SLS), and cetyltrimethylammonium bromide (CTAB). The isolated compounds from Lax of Calotropis gigantea were analyzed using high-performance liquid chromatography. To confirm the encapsulation efficiency and in vitro drug release of the carriers, doxorubicin (DOX) was used as a model natural drug. The hybrid nanocarriers were successfully synthesized through simple solvent evaporation using three surfactants, and the morphology was characterized by SEM and TEM technique. The functionality and crystalline nature of the nanocarriers were confirmed using FTIR and XRD, respectively. Within 90min, the maximum amount of DOX was encapsulated in the carriers, and prolonged cumulative drug release by the nanocarriers was observed. The formulated natural carriers were found to have potentially effective cytotoxic effects on lung cancer cells.

Development of cholate conjugated hybrid polymeric micelles for FXR receptor mediated effective site-specific delivery of paclitaxel

The aim of the present study was to explore the tumor targeting potential of a cholic acid (CA) conjugated polymeric micelle system for the effective delivery of paclitaxel (PTX). CA has a high binding affinity to the farnesoid X receptor (FXR) which is overexpressed in most breast cancer cells. CA grafted poly(bis(carboxyphenoxy)phosphazene)–poly(diallyldimethylammonium chloride) (PCPP–PDADMAC) micelles were prepared by nanoprecipitation in the presence of a surfactant. The polymeric nano micelles (PNMs) exhibited well-defined spherical morphology with a hydrodynamic diameter of around 218 nm. CA incorporated hybrid polymeric micelles form a strong gel at body temperature and exhibit prolonged drug release. In addition, the surface charge of the micelles undergoes positive to negative conversion based on the environmental pH. Positively charged nanomaterials promote faster cellular uptake in the cancer acidic milieu. CA formulation specifically targeted the FXR overexpressed in breast cancer for significant progression of the cytotoxicity of PNM with a 2.69-fold increase in comparison to free PTX. γH2AX and comet assays demonstrate efficient cellular uptake, preferential tumor accumulation, and drug release in the cytoplasmic region. This work suggests that the prepared micelle system has a good tumor-targeting ability with reduced systemic toxicity, proving it to be a promising formulation for breast cancer therapy.

Silver nanoparticle functionalized CS-g-(CA-MA-PZA) carrier for sustainable anti-tuberculosis drug delivery

Recently, drug functionalized biodegradable polymers have been appreciated to be imperative to fabricate multi-drug delivery nanosystems for sustainable drug release. In this work, amphiphilic chitosan-grafted-(cetyl alcohol-maleic anhydride-pyrazinamide) (CS-g-(CA-MA-PZA)) was synthesized by multi-step reactions. The incorporation of rifampicin (RF) and entrapment of silver nanoparticles (Ag NPs) on CS-g-(CA-MA-PZA) polymer was carried out by dialysis technique. From the FT-IR experiment, the polymer modification, incorporation of drugs and the entrapment of Ag NPs on micelles were confirmed. The surface morphology of Ag NPs, polymeric system and drug loaded micelles was described by SEM, TEM and AFM techniques. In addition, the controlled release behaviour of CS-g-(CA-MA-PZA) micelles was studied by UV-Vis spectroscopy. In vitro cell viability, cell apoptosis and cellular uptake experiments shows that multi-drug delivery system could enhance the biocompatibility and higher the cytotoxicity effect on the cells. Since the prepared amphiphilic polymeric micelles exhibit spotty features and the system is a promising strategy for a novel candidate for immediate therapeutically effects for alveolar macrophages.

Sericin-chitosan doped maleate gellan gum nanocomposites for effective cell damage in Mycobacterium tuberculosis

Polysaccharides are increasingly used as biodegradable nanocarrier to selectively deliver therapeutic agents to specific cells. In this study, maleate gellan gum (MA-GG) formed by addition of free radical polymerizable groups, which can be polymerized presence of acetone to design biodegradable three-dimensional networks, were synthesized by esterification. Natural silk sericin was grafted over the maleate gellan gum surface. Maleate Gellan Gum- Silk Sericin-Chitosan (MA-GG-SS-CS) nanocomposites loaded with rifampicin (RF) and pyrazinamide (PZA) to overcome the problems associated with Tuberculosis (TB) therapy. The pH responsive behavior of gellan gum nanocomposites was reposed by silk sericin and exhibited sustained release of 79% RF and 82% PZA for 120 h at pH 4.0. The designed formulations shows higher antimycobacterial activity and rapid delivery of drugs at TB infected macrophage. Nanomaterial effectively aggregated and internalized into the bacterial cells and MH-S cells. Dual drug release inside the cells makes damage in the cell membrane. Green nanocomposites studies pave the way for important use of macromolecules in pulmonary delivery TB drugs.