pH-responsive and targeted delivery of chrysin via folic acid-functionalized mesoporous silica nanocarrier for breast cancer therapy.

Cancer is a disease of global importance. In order to mitigate conventional chemotherapy-related side effects, phytochemicals with inherent anticancer efficacy have been opted. However, the use of nanotechnology is essential to enhance the bioavailability and therapeutic efficacy of these phytochemicals. Herein, we have formulated folic acid conjugated polyacrylic acid capped mesoporous silica nanoparticles (∼47.6 nm in diameter) for pH-dependent targeted delivery of chrysin to breast cancer (MCF-7) cells. Chrysin loaded mesoporous silica nanoparticles (Chr- mSiO2@PAA/FA) have been noted to induce apoptosis in MCF-7 cells through oxidative insult and mitochondrial dysfunction with subsequent G1 arrest. Further, in tumor bearing mice, intravenous incorporation of Chr-mSiO2@PAA/FA has been noticed to enhance the anti-neoplastic effects of chrysin via tumor site-specific accumulation. Enhanced cytotoxicity of chrysin contributed towards in vivo tumor regression, restoration of normalized tissue architecture and maintenance of healthy body weight. Besides, no serious systemic toxicity was manifested in response to Chr-mSiO2@PAA/FA administration in vivo. Thus, the study evokes about the anticancer potentiality of chrysin and its increased therapeutic activity via incorporation into folic acid conjugated mesoporous silica nanoparticles, which may hold greater impact in field of future biomedical research.

Fabrication of phenyl boronic acid modified pH-responsive zinc oxide nanoparticles as targeted delivery of chrysin on human A549 cells.

Recently, different natural bioactive compounds have been used as anticancer agents for their various therapeutic benefits and non-toxic nature to other organs. However, they have various restrictions in preclinical and clinical studies due to their non-targeting nature and insufficient bioavailability. As a result, a zinc oxide nanoparticle (ZnO) based drug delivery medium was constructed which has good bio-compatibility and bio-degradability. It also displays cancer cell-specific drug delivery in a targeted and controlled way. In the present study, phenylboronic acid (PBA) tagged ZnO nanoparticles (ZnO-PBA) was fabricated and in the next step, chrysin (a natural bio-active molecule) was loaded to it to form the nanoconjugate (ZnO-PBA-Chry). Different characterization techniques were used to confirm the successful fabrication of ZnO-PBA-Chry. PBA-tagging to the nanoparticle helps in targeted delivery of chrysin in lung cancer cells (A549) as PBA binds with sialic acid receptors which are over-expressed on the surface of A549 cells. As ZnO dissociates in acidic pH, it shows stimuli-responsive release of chrysin in tumor microenvironment. Application of ZnO-PBA-Chry nanohybrid in lung cancer cell line A549 caused oxidative stress mediated intrinsic cell death and cell cycle arrest. ZnO-PBA-Chry downregulated MMP-2 and VE-Cadherin, thereby inhibiting metastasis and the invasive property of A549 cells.

Synthesis of carbon dots from taurine as bioimaging agent and nanohybrid with ceria for antioxidant and antibacterial applications.

Here we have synthesized water soluble and biocompatible carbon dots (CDs) from taurine via thermal decomposition method. The CDs showed nearly spherical shape with diameter less than 10 nm. The CDs exhibited excitation dependent fluorescence emission and could be used for mammalian cell imaging. The CDs showed excellent DPPH and hydrogen peroxide radical scavenging activity in cell free system. Besides, the CDs also displayed significant intracellular radical scavenging activity in human normal kidney epithelial (NKE) cells. Furthermore, nanohybrids consisting of both CDs and nanoceria (CeO2) were prepared and tested for their biomedical applications. The nanohybrids showed significant antioxidant activities in both cell free and intracellular conditions. The CDs and nanohybrids possessed very little toxicity upto the concentration of 100 µg/mL when treated for 24 hours in human NKE cells. The CDs as well as nanohybrids further displayed significant bacterial growth inhibition against both gram-positive and gram-negative bacteria under dark as well as light illumination condition via the bacterial membrane damage. However, under the light illumination, the bacterial growth inhibition of CDs and nanohybrids was further enhanced due to the generation of reactive oxygen radicals and subsequent DNA degradation. A higher dose-dependent intracellular antioxidant and antibacterial activities of the nanohybrid is attributed to the synergistic effect of nanoceria and CDs. All these results clearly reflected that our synthesized CDs and their nanohybrids can be used for several biomedical applications.

Enhancement of anti-neoplastic effects of cuminaldehyde against breast cancer via mesoporous silica nanoparticle based targeted drug delivery system.

AIMS: Synthesis of novel drug delivery system for targeted delivery of cuminaldehyde to breast cancer cells and the subsequent analyses of anti-neoplastic potential of the drug. MAIN METHODS: 3-carboxy-phenyl boronic acid (PBA) conjugated and polyacrylic acid (PAA) gated mesoporous silica nanoparticles (MSNs) were synthesized for the targeted delivery of cuminaldehyde (CUM) to breast cancer cells. Enhancement of anti-neoplastic effects of cuminaldehyde (4-isopropylbenzaldehyde) by the nanoconjugates was assessed. KEY FINDINGS: The anti-cancer effects of non-targeted and targeted drug-nanoconjugates were examined in vitro and in vivo. The targeted drug-nanoconjugates caused cell cycle arrest and induced the intrinsic pathway of apoptosis in MCF-7 cells through mitochondrial damage. In vivo intravenous injection of the targeted drug-nanoconjugates led to effective reduction in growth of 4 T1 induced mammary pad tumor in female BALB/c mice via augmented accumulation of cuminaldehyde. The drug-nanoconjugates did not exhibit any systemic toxicity. SIGNIFICANCE: Therefore, MSN-PBA-CUM-PAA represents a potent therapeutic model for breast cancer treatment.

Non-Markovianity between Site Pairs in FMO Complex Using Discrete-Time Quantum Jump Model.

The Fenna-Mathews-Olson (FMO) complex present in green sulfur bacteria is known to mediate the transfer of excitation energy between light-harvesting chlorosomes and membrane-embedded bacterial reaction centers. Due to the high efficiency of this transport process, it is an extensively studied pigment-protein complex system with the eventual aim of modeling and engineering similar dynamics in other systems and using it for real-time application. Some studies have attributed the enhancement of transport efficiency to wavelike behavior and non-Markovian quantum jumps resulting in long-lived and revival of quantum coherence, respectively. Since dynamics in these systems reside in the quantum-classical regime, quantum simulation of such dynamics will help in exploring the subtle role of quantum features in enhancing the transport efficiency, which has remained unsettled. Discrete simulation of the dynamics in the FMO complex can help in efficient engineering of the heat bath and controlling the environment with the system. In this work, using the discrete quantum jump model we show and quantify the presence of higher non-Markovian memory effects in specific site pairs when internal structures and environmental effects are in favor of faster transport. As a consequence, our study leans toward the connection between non-Markovianity in quantum jumps with the enhancement of transport efficiency.

In vivo therapeutic evaluation of a novel bis-lawsone derivative against tumor following delivery using mesoporous silica nanoparticle based redox-responsive drug delivery system.

Herein, we have evaluated the in vivo therapeutic efficacy and systemic toxicity profile of a synthetic anticancer compound [3,3'-((4-(trifluoromethyl)phenyl)methylene)bis(2-hydroxynaphthalene-1,4-dione)]. A multifunctional mesoporous silica nanoparticle (MSN) based drug delivery network was also fabricated which specifically showed targeting nature towards the cancer cell. The mesopores of silica nanoparticles were tagged with phenyl boronic acid (PBA) for targeted drug delivery into tumor tissue. 1j was then loaded inside the nanocarriers followed by pore blocking with gold nanoparticles (GN) to attain a redox-responsive controlled drug delivery pattern. The synthesized nanocarriers (1j@-MSN-PBA-GN) having mean diameter of ~86 nm exhibited a moderate 1j loading content of 13.68% with overall negative surface charge. Both the targeted and non-targeted nanoformulations were tested for their anticancer activities both in vitro and in vivo models, and found more effective as compared with free 1j treatment. However, the targeted nanoformulations showed higher therapeutic effect due to increased cellular internalization and caused mitochondria-dependent apoptosis in MCF-7 cells via oxidative stress. Besides, the targeted nanoformulation significantly inhibited in the development of solid tumor in comparison to non-targeted nanoformulations and free 1j as a consequence of increased internalization of the drug-candidate in tumor tissue. Therefore, this study proposes that 1j can be considered as a potent anti-carcinogenic compound in vivo and its therapeutic potential is further increased by using PBA functionalized and GN gated MSN-based controlled drug delivery system without showing any significant systemic toxicity.

Targeted delivery of curcumin in breast cancer cells via hyaluronic acid modified mesoporous silica nanoparticle to enhance anticancer efficiency.

Curcumin (C) is a natural antioxidant which has many beneficial effects. However, poor bioavailability and less water solubility render it unsuitable as an anti-cancer drug. Herein, curcumin was delivered through Mesoporous silica nanoparticle (MSN) based drug delivery system to enhance its anticancer efficacy. Targeted delivery of curcumin in cancer cells was also achieved by conjugating hyaluronic acid (HA) on the surface of MSN. HA showed its targeting ability through the binding with CD-44 receptors in cancer cells. The synthesis of MSN-HA-C was verified by used several characterization techniques like TEM, SEM, XRD and DLS. MSN-HA-C showed diameter of ∼ 75 nm with negatively charged surface and drug loading content of 14.76 %. The synthesized nanohybrid showed MDA-MB-231 cell death by the induction of ROS, cell cycle arrest and modulation of NF-κB and Bax mediated apoptotic pathway. The nanohybrid also effectually decreased tumor volume in tumor-bearing mice compared with free C due to the increased bioavailability and higher cellular uptake of C in tumor tissue. Overall, the study offered that MSN-HA-C has increased anticancer efficacy than that of free curcumin.

Tumor targeted delivery of umbelliferone via a smart mesoporous silica nanoparticles controlled-release drug delivery system for increased anticancer efficiency.

Herein, a mesoporous silica nanoparticle (MSN) based biocompatible, targeted and controlled drug delivery system has been synthesized for tumor tissue-specific drug delivery. Umbelliferone, a natural coumarin derivative was loaded into the pores of MSN and capped with pH-sensitive poly acrylic acid (PAA). For targeted delivery of umbelliferone in tumor tissue, folic acid (FA) was grafted onto the surface of drug-loaded and PAA-coated MSN. The successful construction of the nanohybrid (Umbe@MSN-PAA-FA) was confirmed by performing a series of characterization. The synthesized pH-responsive nanohybrid showed diameter of around 50 nm with overall negative surface charge and drug loading content of 12.56%. In vitro study showed that the nanohybrid caused significant cytotoxicity through the induction of both oxidative stress as well as mitochondrial damage in folate receptor over-expressed in human breast cancer cell, MCF-7 compared with free umbelliferone. In vivo study also exhibited that the nanohybrid effectively reduced tumor growth in tumor-bearing mice compared with free umbelliferone due to the enlarged bioavailability of the drug in tumor tissue. Besides, the nanohybrid did not exhibit any significant sign of systemic toxicity in other vital organs. Together, the study denoted that PAA and FA functionalized MSN controlled-drug delivery system could assist to increase the anticancer potential of umbelliferone.

Sonochemically Synthesized Spin-Canted CuFe2O4 Nanoparticles for Heterogeneous Green Catalytic Click Chemistry.

Heterogeneous green catalysis by using magnetically separable nanometal-oxide catalysts has become a subject of prime focus recently. PXRD (powder X-ray diffraction), FESEM (field emission scanning electron microscopy), and HRTEM (high-resolution tunneling electron microscopy) with IR and Raman spectroscopy are applied to analyze the structural and microstructural properties of nanosized (∼15.3 nm) CuFe2O4 synthesized by both sonochemical and mechanochemical processes. The sonochemical process provides a better uniformity of sizes of the nanoparticles (NPs). Rietveld refinement with the PXRD pattern reveals the inverse spinel-like architecture of CuFe2O4 NPs. The Raman spectra also indicate the phase purity of the synthesized material. The static magnetic measurements are performed at different magnetic fields and temperature ranges from 300 to 5 K, which confirms the existence of the ferrimagnetic phase mixed with some finer superparamagnetic (SPM) nanophases within the sample. Unsaturated magnetization is observed even at an applied 5 T magnetic field for the presence of spin-canting nature in the partially inverted copper ferrite phases at the surfaces of the nanoparticles. Now, these coupled magnetic CuFe2O4 NPs are used as a heterogeneous catalyst for three-component Huisgen 1,3-dipolar cycloaddition click reaction in aqueous media. By this catalyst system, we were able to couple alkyl halide, epoxide, or boronic acid with alkynes efficiently to furnish 1,4-disubstituted 1,2,3-triazoles in excellent yields within very short reaction time. The test for heterogeneity, reusability, and reproducibility of the catalyst has also been performed successfully without prominent decrease in yield up to the fifth cycle.

New mononuclear and binuclear oxomolybdenum(V) complexes containing NN chelator: Syntheses, DFT calculations, interaction with BSA protein and in vitro cytotoxic activity.

A neutral bidentate ligand 2-(3-methyl-5-phenyl pyrazol-1-yl) benzthiazole (L) has been synthesized by refluxing equimolar proportions of 2-hydrazino benzthiazole and benzoyl acetone in ethanol. The ligand acts in a NN donor fashion and forms stable mononuclear, MoOX3L [L = Ligand, X = Cl (1), Br (2)] and binuclear Mo2O4X2L2 [L = Ligand, X = Cl (3), Br (4)] complexes with molybdenum(V). The ligand and complexes are thoroughly characterized by elemental analyses, IR, UV-Vis spectroscopy, EPR study, magnetic susceptibility, thermogravimetry and cyclic voltammetry. Magnetic moment measurements reveal that the mononuclear complexes are paramagnetic while the binuclear complexes are diamagnetic in nature. EPR studies also confirm the presence of a mononuclear Mo(V) moiety in the complexes. Relevant Density Functional Theory (DFT) calculations have been carried out to determine the structures of the synthesized compounds. The binding mode and mechanism of interaction of the synthesized compounds with bovine serum albumin (BSA) were studied by concentration dependent absorption and fluorescence titration experiments. The ligand and complexes 1-4 are screened for their potential in vitro anticancer activities against three different human cancer cell lines, namely, cervix adenocarcinoma epithelial cells (HeLa), renal carcinoma cells (SK-RC-45) and breast adenocarcinoma cells (MCF-7). The oxomolybdenum(V) complexes are found to exhibit higher anticancer potency towards the cancer cells than the free ligand. Also, structure activity relationship (SAR) studies of this new series of oxomolybdenum(V) complexes indicate that the anticancer activity is to some extent dependent on the electronic effects of the halogen atom coordinated to the molybdenum centre.

Targeted delivery of quercetin via pH-responsive zinc oxide nanoparticles for breast cancer therapy.

Naturally occurring bioactive compounds are gaining much importance as anti-tumor agents in recent times due to their high therapeutic potential and less systemic toxicity. However, different preclinical and clinical studies have noted significant shortcomings, such as nonspecific tumor targeting and low bioavailability which limit their usage in therapeutics. Therefore, a safe and compatible nanoparticle mediated controlled drug delivery system is in high demand to enable effective transport of the drug candidates in the tumor tissue. Herein, we have synthesized phenylboronic acid (PBA) conjugated Zinc oxide nanoparticles (PBA-ZnO), loaded with quercetin (a bioflavonoid widely found in plants), with zeta potential around -10.2 mV and diameter below 40 nm. Presence of PBA moieties over the nanoparticle surface facilitates targeted delivery of quercetin to the sialic acid over-expressed cancer cells. Moreover, Quercetin loaded PBA-ZnO nanoparticles (denoted as PBA-ZnO-Q) showed pH responsive drug release behavior. Results suggested that PBA-ZnO-Q induced apoptotic cell death in human breast cancer cells (MCF-7) via enhanced oxidative stress and mitochondrial damage. In line with the in vitro results, PBA-ZnO-Q was found to be effective in reducing tumor growth in EAC tumor bearing mice. Most interestingly, PBA-ZnO-Q is found to reduce tumor associated toxicity in liver, kidney and spleen. The cytotoxic potential of the nanohybrid is attributed to the combinatorial cytotoxic effects of quercetin and ZnO in the cancer cells. Overall, the presented data highlighted the chemotherapeutic potential of the novel nanohybrid, PBA-ZnO-Q which can be considered for clinical cancer treatment.

pH-responsive and targeted delivery of curcumin via phenylboronic acid-functionalized ZnO nanoparticles for breast cancer therapy.

Nanoparticle-mediated targeted delivery of bioactive natural compounds has recently been gaining much interest for breast cancer therapy. Herein, phenyl boronic acid (PBA)-conjugated and pH-responsive ZnO nanoparticles (diameter ∼40 nm) were synthesized for the tumor tissue-specific delivery of curcumin. PBA conjugation facilitates the targeted delivery of curcumin to the sialic acid overexpressed in breast cancer cell membranes. Curcumin-loaded ZnO nanoparticles (ZnO-PBA-Curcumin) caused apoptotic cell death in MCF-7 human breast cancer cells by inducing oxidative stress and mitochondrial damage. Further, in vivo intravenous (i.v.) administration of ZnO-PBA-Curcumin was found to effectively decrease tumor growth in Ehrlich ascites carcinoma (EAC) tumor-bearing mice via the enhanced accumulation of curcumin. Interestingly, ZnO-PBA-Curcumin did not show any signs of systemic toxicity. The cytotoxic potential of the nanohybrid ZnO-PBA-Curcumin is attributed to the combinatorial cytotoxic effects of curcumin and ZnO in cancer cells. Collectively, ZnO-PBA-Curcumin may represent a potential treatment modality for breast cancer therapy. This study provides insight into the tumor cell targeting mechanism using PBA functionalization, and the anticancer efficacy of curcumin-loaded pH-sensitive nanohybrids can be attributed to the differential oxidative stress-inducing properties of curcumin and Zn+2 ions.

Microwave induced synthesis of ZnO nanorods and their efficacy as a drug carrier with profound anticancer and antibacterial properties.

In the present study, we report the microwave-induced synthesis of fluorescent zinc oxide nanorods (ZnO) and their usage as a cargo material to carry hydrophobic drug, quercetin. TEM and SEM showed the rod-shape morphology of our synthesized ZnO. XRD showed several diffraction peaks correspond to a hexagonal wurtzite structure. The optical and chemical natures of these nanorods were also confirmed from the UV-vis (showed a distinct absorption bands from 361 to 395 nm) and FTIR spectrum (showed absorption band specific to Zn-O stretching). The synthesized ZnO also showed fluorescence emission at around 550 nm when excited under UV irradiation. Quercetin was loaded onto ZnO surface via employing a metal ion-ligand coordination bond, (ZnO/QR), which exhibit pH-sensitive release behavior. ZnO/QR displayed superior drug loading content (42%) and loading efficiency (72.4%). in vitro assays showed that ZnO/QR exhibited higher anticancer, as well as antibacterial activities compared with free quercetin and ZnO. All these results highlight the synthesis of ZnO nanorods under microwave irradiation, which can be used as a plausible therapeutic option for bioimaging and drug delivery purpose.

Prophylactic role of taurine and its derivatives against diabetes mellitus and its related complications.

Taurine is a conditionally essential amino acid present in the body in free form. Mammalian taurine is synthesized in the pancreas via the cysteine sulfinic acid pathway. Anti-oxidation and anti-inflammation are two main properties through which it exerts its therapeutic effects. Many studies have shown its excellent therapeutic potential against diabetes mellitus and related complications like diabetic neuropathy, retinopathy, nephropathy, hematological dysfunctions, reproductive dysfunctions, liver and pancreas related complications etc. Not only taurine, a number of its derivatives have also been reported to be important in ameliorating diabetic complications. The present review has been aimed to describe the importance of taurine and its derivatives against diabetic metabolic syndrome and related complications.

Visceral leishmaniasis or systemic lupus erythematosus flare?

Systemic lupus erythematosus (SLE) is a multisystem disorder characterised by B-cell hyperactivity with production of multiple autoantibodies. Fever in SLE may be caused by disease exacerbation or by infection. We report a patient of SLE that was later complicated by fever, pancytopenia, and massive splenomegaly. Corticosteroid therapy for SLE might have masked the underlying infection at earlier stage. Despite negative results of rk-39 test and bone marrow biopsy, a very high suspicion for visceral leishmaniasis (VL) led us to go for direct agglutination test (DAT) and polymerase chain reaction (PCR) for leishmanial antigen that revealed positive results. Moreover, significant improvement in clinical and biochemical parameters was noted on starting the patient on antileishmanial therapy.