Chlorotoxin modified morusin-PLGA nanoparticles for targeted glioblastoma therapy.

Malignant brain tumors remain a major cause of concern and mortality as successful treatment is hindered due to the poor transport and low penetration of chemotherapeutics across the blood-brain barrier (BBB). In this study, a nano formulation composed of chlorotoxin (CTX)-conjugated morusin loaded PLGA nanoparticles (PLGA-MOR-CTX) was devised against Glioblastoma Multiforme (GBM) and its anti-proliferative effects were evaluated in vitro. The synthesized nanoparticles were loaded with morusin, a naturally derived chemotherapeutic drug, and surface conjugated with CTX, a peptide derived from scorpion venom, highly specific for chloride channels (CIC-3) expressed in glioma tumor cells, as well as for matrix metalloproteinase (MMP-2), which is up regulated in the tumor microenvironment. Subsequently, the anti-cancer potential of the NPs was assessed in U87 and GI-1 (human glioblastoma) cells. Antiproliferative, cell apoptosis, and other cell-based assays demonstrated that the PLGA-MOR-CTX NPs resulted in enhanced inhibitory effects on U87 and GI-1 glioma cells. Prominent cytotoxicity parameters such as ROS generation, enhanced caspase activity, cytoskeletal destabilization, and inhibition of MMP-activity were observed in glioblastoma cells upon PLGA-MOR-CTX NP treatment. The cytocompatibility observed with normal human neuronal cells (HCN-1A) and the enhanced lethal effects in glioblastoma cells highlight the potential of PLGA-MOR-CTX nanoparticles as promising therapeutic nanocarriers towards GBM.

Gold nanocages entering into the realm of high-contrast photoacoustic ocular imaging.

Bioinert gold nanoparticles of various shapes and functionalities are widely accepted as contrast agents (CAs) for several modalities of imaging, viz., electron microscopy, computerized tomography (CT), X-ray and photoacoustic (PA) imaging. However, testing of novel compact-imaging probes for ocular diagnostic imaging is always challenging. Here, ultra-fast microwave oven synthesized gold nanocages (AuNcgs) were successfully demonstrated for high-contrast PA ocular imaging for the first time. Methods are described for the synthesis, characterization and application of quickly synthesized AuNcgs in diagnostic ocular imaging. PA and ultrasound (US) images were acquired using a commercial US imaging scanner integrated with a tunable nanosecond pulsed laser. This integrated hybrid-modality system is a combined PA and US platform for imaging which enabled acquiring of complementary structural and optical absorption-based information simultaneously. Initial experiments were conducted using tubings filled with solutions of different concentrations of quickly synthesized AuNcgs. Biological PA and US imagings were demonstrated using enucleated porcine eye samples. Based on the acquired results, it is envisaged that AuNcgs can be employed as a high strength PA CA to potentially diagnose ocular disease like uveal melanoma in the near future.

Heat-Shock Protein 90-Targeted Nano Anticancer Therapy.

Suboptimal chemotherapy of anticancer drugs may be attributed to a variety of cellular mechanisms, which synergize to dodge the drug responses. Nearly 2 decades of heat-shock protein 90 (Hsp90)-targeted drug discovery has shown that the mono-therapy with Hsp90 inhibitors seems to be relatively ineffective compared with combination treatment due to several cellular dodging mechanisms. In this article, we have tried to analyze and review the Hsp90 and mammalian target of rapamycin (m-TOR)-mediated drug resistance mechanisms. By using this information we have discussed about the rationale behind use of drug combinations that includes both or any one of these inhibitors for cancer therapy. Currently, biodegradable nano vector (NV)-loaded novel drug delivery systems have shown to resolve the problems of poor bioavailability. NVs of drugs such as paclitaxel, doxorubicin, daunorubicin, and others have been successfully introduced for medicinal use. Hence, looking at the success of NVs, in this article we have also discussed the progress made in the delivery of biodegradable NV-loaded Hsp90 and m-TOR-targeted inhibitors in multiple drug combinations. We have also discussed the possible ways by which the market success of biodegradable NVs can positively impact the clinical trials of anti-Hsp90 and m-TOR combination strategy.

Plasmonic fluorescent CdSe/Cu2S hybrid nanocrystals for multichannel imaging and cancer directed photo-thermal therapy.

A simple, crude Jatropha curcas (JC) oil-based synthesis approach, devoid of any toxic phosphine and pyrophoric ligands, to produce size and shape tuned CdSe QDs and a further copper sulfide (Cu2S) encasing is presented. The QDs exhibited excellent photoluminescent properties with narrow band gap emission. Furthermore, the Cu2S shell rendered additional cytocompatibility and stability to the hybrid nanomaterial, which are major factors for translational and clinical applications of QDs. The nanocomposites were PEGylated and folate conjugated to augment their cytoamiability and enhance their specificity towards cancer cells. The nanohybrids possess potentials for visible, near infrared (NIR), photoacoustic (PA) and computed tomography (µCT) imaging. The diverse functionality of the composite was derived from the multi-channel imaging abilities and thermal competence on NIR laser irradiation to specifically actuate the photo-thermal ablation of brain cancer cells.

FITC/suramin harboring silica nanoformulations for cellular and embryonic imaging/anti-angiogenic theranostics.

The in vitro and in vivo uptake, toxicological analysis and anti-angiogenic theranostic prospect of FITC loaded (FITC-Si) and suramin loaded (Sur-Si) silica nanoparticles are presented. FITC/suramin encapsulated silica nanoparticles (NPs) with an average size of <30 nm were synthesized. The uptake of FITC-Si by human umbilical vein endothelial cells (HuVECs) (in vitro) and by early stage medaka embryos (in vivo) was monitored by fluorescence microscopy. The nanoformulation was found to be biocompatible with both cells and embryos. The cytotoxicity analysis, tubulogenesis and migration assay confirmed the anti-angiogenic potential of Sur-Si NPs in HuVECs. The imaging of medaka embryos exposed to FITC-Si, their survival and hatching rate and biocompatibility post FITC-Si exposure were documented. The in vivo drug delivery mediated anti-angiogenic potential of Sur-Si NPs was assessed by survival and hatching rate analysis along with morphological indicators. At higher concentrations, Sur-Si proved lethal to embryos, whereas at lower concentrations it was rather an efficient anti-angiogenic formulation leading to malformed vasculogenesis and inhibited intersegmental vessel formation in an efficient dose dependent mode. The results indicate the potential application of such nanoformulation in future anti-angiogenic theranostics.

Biocompatible nanofibers based on extremophilic bacterial polysaccharide, Mauran from Halomonas maura.

Extremophilic bacterial polysaccharide based biocompatible nanofibers were produced for the first time via electrospinning technique. Mauran (MR), an extremophilic sulfated exopolysaccharide was extracted from moderately halophilic bacterium, Halomonas maura and characterized for the application of nanofiber synthesis. Thin-uniform MR nanofibers were produced using homogenous solutions of poly (vinyl alcohol) (PVA) blended with different concentrations of MR. Characterization of complex MR/PVA nanofibers were performed using scanning electron microscope and analyzed for the cytotoxicity using mouse fibroblast cells as well as mesenchymal stem cells. An average of 120 nm sized nanofibers were produced and tested for an enhanced cell growth under in vitro conditions in comparison with control. MR and MR/PVA nanofibers were found to be an excellent biomaterial for the migration, proliferation and differentiation of mammalian cells, which was confirmed by cell adhesion studies and confocal microcopy. Interestingly, biological and physicochemical properties of MR hasten the application of MR based nanofibers for various biomedical applications like tissue engineering and drug delivery.

Aptamer conjugated magnetic nanoparticles as nanosurgeons.

Magnetic nanoparticles have shown promise in the fields of targeted drug delivery, hyperthermia and magnetic resonance imaging (MRI) in cancer therapy. The ability of magnetic nanoparticles to undergo surface modification and the effect of external magnetic field in the dynamics of their movement make them an excellent nanoplatform for cancer destruction. Surgical removal of cancerous or unwanted cells selectively from the interior of an organ or tissue without any collateral damage is a serious problem due to the highly infiltrative nature of cancer. To address this problem in surgery, we have developed a nanosurgeon for the selective removal of target cells using aptamer conjugated magnetic nanoparticles controlled by an externally applied three-dimensional rotational magnetic field. With the help of the nanosurgeon, we were able to perform surgical actions on target cells in in vitro studies. LDH and intracellular calcium release assay confirmed the death of cancer cells due to the action of the nanosurgeon which in turn nullifies the possibility of proliferation by the removed cells. The nanosurgeon will be a useful tool in the medical field for selective surgery and cell manipulation studies. Additionally, this system could be upgraded for the selective removal of complex cancers from diverse tissues by incorporating various target specific ligands on magnetic nanoparticles.

Template-assisted synthesis and characterization of passivated nickel nanoparticles.

Potential applications of nickel nanoparticles demand the synthesis of self-protected nickel nanoparticles by different synthesis techniques. A novel and simple technique for the synthesis of self-protected nickel nanoparticles is realized by the inter-matrix synthesis of nickel nanoparticles by cation exchange reduction in two types of resins. Two different polymer templates namely strongly acidic cation exchange resins and weakly acidic cation exchange resins provided with cation exchange sites which can anchor metal cations by the ion exchange process are used. The nickel ions which are held at the cation exchange sites by ion fixation can be subsequently reduced to metal nanoparticles by using sodium borohydride as the reducing agent. The composites are cycled repeating the loading reduction cycle involved in the synthesis procedure. X-Ray Diffraction, Scanning Electron Microscopy, Transmission Electron microscopy, Energy Dispersive Spectrum, and Inductively Coupled Plasma Analysis are effectively utilized to investigate the different structural characteristics of the nanocomposites. The hysteresis loop parameters namely saturation magnetization and coercivity are measured using Vibrating Sample Magnetometer. The thermomagnetization study is also conducted to evaluate the Curie temperature values of the composites. The effect of cycling on the structural and magnetic characteristics of the two composites are dealt in detail. A comparison between the different characteristics of the two nanocomposites is also provided.

On the dielectric dispersion and absorption in nanosized manganese zinc mixed ferrites.

The temperature and frequency dependence of dielectric permittivity and dielectric loss of nanosized Mn(1-x)Zn(x)Fe(2)O(4) (for x = 0, 0.2, 0.4, 0.6, 0.8, 1) were investigated. The impact of zinc substitution on the dielectric properties of the mixed ferrite is elucidated. Strong dielectric dispersion and broad relaxation were exhibited by Mn(1-x)Zn(x)Fe(2)O(4). The variation of dielectric relaxation time with temperature suggests the involvement of multiple relaxation processes. Cole-Cole plots were employed as an effective tool for studying the observed phenomenon. The activation energies were calculated from relaxation peaks and Cole-Cole plots and found to be consistent with each other and indicative of a polaron conduction.

Surface modification of poly(ethylene terephthalate) by plasma polymerization of poly(ethylene glycol).

Poly(ethylene glycol) (PEG) was 'polymerized' onto poly(ethylene terephthalate) (PET) surface by radio frequency (RF) plasma polymerization of PEG (average molecular weight 200 Da) at a monomer vapour partial pressure of 10 Pa. Thin films strongly adherent onto PET could be produced by this method. The modified surface was characterized by infra red (IR) spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), cross-cut test, contact angle measurements and static platelet adhesion studies. The modified surface, believed to be extensively cross-linked, however showed all the chemical characteristics of PEG. The surface was found to be highly hydrophilic as evidenced by an interfacial free energy of about 0.7 dynes/cm. AFM studies showed that the surface of the modified PET became smooth by the plasma polymerized deposition. Static platelet adhesion studies using platelet rich plasma (PRP) showed considerably reduced adhesion of platelets onto the modified surface by SEM. Plasma 'polymerization' of a polymer such as PEG onto substrates may be a novel and interesting strategy to prepare PEG-like surfaces on a variety of substrates since the technique allows the formation of thin, pin-hole free, strongly adherent films on a variety of substrates.

Evidence for intergranular tunnelling in polyaniline passivated α-Fe nanoparticles.

Nanoparticles are of immense importance both from the fundamental and application points of view. They exhibit quantum size effects which are manifested in their improved magnetic and electric properties. Mechanical attrition by high energy ball milling (HEBM) is a top down process for producing fine particles. However, fineness is associated with high surface area and hence is prone to oxidation which has a detrimental effect on the useful properties of these materials. Passivation of nanoparticles is known to inhibit surface oxidation. At the same time, coating polymer film on inorganic materials modifies the surface properties drastically. In this work a modified set-up consisting of an RF plasma polymerization technique is employed to coat a thin layer of a polymer film on Fe nanoparticles produced by HEBM. Ball-milled particles having different particle size ranges are coated with polyaniline. Their electrical properties are investigated by measuring the dc conductivity in the temperature range 10-300 K. The low temperature dc conductivity (I-V) exhibited nonlinearity. This nonlinearity observed is explained on the basis of the critical path model. There is clear-cut evidence for the occurrence of intergranular tunnelling. The results are presented here in this paper.