Ya-Jen Chang

Biodistribution and pharmacokinetics of 188Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice.

Background Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR) effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT) image, dosimetry, and therapeutic efficacy of 188Re-labeled nanoliposomes (188Re-liposomes) in a C26 colonic peritoneal carcinomatosis mouse model were evaluated. Methods Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered 188Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of 188Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM® computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with 188Re-liposomes and 5-fluorouracil (5-FU), respectively, were evaluated and compared. Results In biodistribution, the highest uptake of 188Re-liposomes in tumor tissues (7.91% ± 2.02% of the injected dose per gram of tissue [%ID/g]) and a high tumor to muscle ratio (25.8 ± 6.1) were observed at 24 hours after intravenous administration. The pharmacokinetics of 188Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h). Micro-SPECT/CT imaging of 188Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with images from autoradiography and biodistribution data. Dosimetry study revealed that the 188Re-liposomes did not cause high absorbed doses in normal tissue but did in small tumors. Radiotherapeutics with 188Re-liposomes provided better survival time (increased by 34.6% of life span; P < 0.05), tumor and ascites inhibition (decreased by 63.4% and 83.3% at 7 days after treatment; P < 0.05) in mice compared with chemotherapeutics of 5-fluorouracil (5-FU). Conclusion The use of 188Re-liposomes for passively targeted tumor therapy had greater therapeutic effect than the currently clinically applied chemotherapeutics drug 5-FU in a colonic peritoneal carcinomatosis mouse model. This result suggests that 188Re-liposomes have potential benefit and are safe in treating peritoneal carcinomatasis of colon cancer.

Comparative Therapeutic Efficacy of Rhenium-188 Radiolabeled-Liposome and 5-Fluorouracil in LS-174T Human Colon Carcinoma Solid Tumor Xenografts

Nanoliposomes are important carriers capable of packaging drugs for various delivery applications. Rhenium-188-radiolabeled liposome ((188)Re-liposome) has potential for radiotherapy and diagnostic imaging. To evaluate the targeting of (188)Re-liposome, biodistribution, microSPECT/CT, whole-body autoradiography (WBAR), and pharmacokinetics were performed in LS-174T human tumor-bearing mice. The comparative therapeutic efficacy of (188)Re-liposome and 5-fluorouracil (5-FU) was assessed according to inhibition of tumor growth and the survival ratio. The highest uptake of (188)Re-liposome in LS-174T tumor was found at 24 hours by biodistribution and microSPECT/CT imaging, showing a positive correlation for tumor targeting of (188)Re-liposome using the Pearsons correlation analysis (r=0.997). Pharmacokinetics of (188)Re-liposome showed the properties of high circulation time and high bioavailability (mean residence time [MRT]=18.8 hours, area under the curve [AUC]=1371%ID/g·h). For therapeutic efficacy, the tumor-bearing mice treated with (188)Re-liposome (80% maximum tolerated dose [MTD], 23.7 MBq) showed better tumor growth inhibition and longer survival time than those treated with 5-FU (80% MTD, 144 mg/kg). The median survival time for mice treated with (188)Re-liposome (58.5 days; p<0.05) was significantly better than those of 5-FU (48.25 days; p>0.05) and normal saline-treated mice (43.63 days). Dosimetry study revealed that the (188)Re-liposome did not lead to high absorbed doses in normal tissue, but did in small tumors. These results of imaging and biodistribution indicated the highly specific accumulation of tumor after intravenous (i.v.) injection of (188)Re-liposome. The therapeutic efficacy of radiotherapeutics of (188)Re-liposome have been confirmed in a LS-174T solid tumor animal model, which points to the potential benefit and promise of passive nanoliposome delivered radiotherapeutics for cancer treatment.

Preliminary evaluation of acute toxicity of 188Re–BMEDA–liposome in rats

Liposomes can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. To evaluate therapeutic strategies, it is essential to use animal models reflecting important safety aspects before clinical application. The objective of this study was to investigate acute radiotoxicity of 188Re‐N,N‐bis (2‐mercaptoethyl)‐N′,N′‐diethylethylenediamine (BMEDA)‐labeled pegylated liposomes (188Re–BMEDA–liposome) in Sprague–Dawley rats. Rats were administered with 188Re–BMEDA–liposome, normal saline as blank or non‐radioactive liposome as vehicle control via intravenous injection and observed for 14 days. Examinations were conducted with respect to mortality, clinical signs, food consumption, body weight and hematological and biochemical analyses. In addition, gross necropsy, histopathological examinations and cytogenetic analyses were also performed. None of the rats died and no clinical sign was observed during the 14‐day study period. Rats administered with 188Re–BMEDA–liposome at dosage of 185 MBq displayed a significant weight loss compared with the control from study day (SD) 1 to SD 4, and the white blood cell count reduced to 5–10% of initial value (female: 18.55 ± 6.58 to 0.73 ± 0.26 × 103 µl−1; male: 14.52 ± 5.12 to 1.43 ± 0.54 × 103 µl−1) 7 days‐post injection, but were found to have recovered on SD 15. There were no significant differences in biochemical parameters and histopathological assessments between the 188Re–BMEDA–liposome‐treated and control groups. The frequencies of dicentric chromosomes were associated with dosage of 188Re–BMEDA–liposome. The information generated from this study on acute toxicity will serve as a safety reference for further subacute toxicity study in rats and human clinical trials. Copyright

Molecular imaging and therapeutic efficacy of 188Re-(DXR)-liposome-BBN in AR42J pancreatic tumor-bearing mice

Liposomes are good candidates as drug carriers and have been widely investigated in drug delivery systems. In this study, a new combination of bimodal 188Re-(DXR)-liposome-BBN radiochemotherapeutics was designed and studied for treating solid pancreatic tumor by intravenous administration. The in vivo nuclear microSPECT/CT imaging of tumor targeting, prolonged survival time and therapeutic efficacy were evaluated in AR42J malignant pancreatic solid tumor-bearing nude mice. MicroSPECT/CT imaging of 188Re-liposome-BBN pointed to significant targeting in tumors at 24 h after intravenous injection (SUV=2.13 ± 0.98). Co-injection of a blocking dose of cold BBN (4 mg/kg) inhibited the accumulation of 188Re-liposome-BBN in tumors (SUV=1.82 ± 0.31). For therapeutic efficacy, inhibition of tumor growth in mice treated with 188Re-DXR-liposome-BBN was precisely controlled [mean growth inhibition rate (MGI) = 0.092] and had longer survival time [life-span (LS) = 86.96%] than those treated with anticancer drug 188Re-liposome-BBN (MGI = 0.130; LS = 75%), Lipo-Dox-BBN (MGI = 0.666; LS = 3.61%) and untreated control mice. An additive tumor regression effect was observed (CI 0.946) for co-delivery of 188Re-DXR-liposome-BBN radiochemotherapeutics. These results point to the potential benefit of the 188Re-(DXR)-liposome-BBN radiochemotherapeutics for adjuvant cancer treatment with applications in oncology.

Pharmacokinetics and Dosimetry of 111In/188Re-Labeled PEGylated Liposomal Drugs in Two Colon Carcinoma-Bearing Mouse Models

PEGylated liposomes are important drug carriers for nanomedicine cancer therapy. PEGylated liposomes can encapsulate radio- and chemo-drugs and passively target tumor sites via enhanced permeability and retention effect. This study estimated the pharmacokinetics and dosimetry after administration of radio-chemotherapeutics ((111)In-labeled vinorelbine [VNB]-encapsulated liposomes, InVNBL, and (188)Re-labeled doxorubicin [DXR]-encapsulated liposomes, ReDXRL) for radionuclide therapy in two colon carcinoma-bearing mouse models. A C26 colon carcinoma tumor/ascites mouse model and a subcutaneous solid tumor-bearing mouse model were employed. Biodistribution studies of InVNBL and ReDXRL after intraperitoneal administration in tumor/ascites-bearing mice (protocol A) and intravenous administration in subcutaneous solid tumor-bearing mice (protocol B) were performed. The radiation dose to normal tissues and tumors were calculated based on the results of distribution studies in mice, using the OLINDA/EXM program. The cumulated activities in most organs after administration of InVNBL in either the tumor/ascites-bearing mice (protocol A) or the subcutaneous solid tumor-bearing mice (protocol B) were higher than those of ReDXRL. Higher tumor-to-normal-tissues absorption dose ratios (T/NTs) were observed after administration of InVNBL than those of ReDXRL for protocol A. The T/NTs for the liver, spleen, and red marrow after injection of InVNBL for protocol B were similar to those of ReDXRL. The critical organ was found to be red marrow, and thus the red marrow absorption dose defined the recommended maximum administration activity of these liposomal drugs. Characterization of pharmacokinetics and dosimetry is needed to select the appropriate radiotherapeutics for specific tumor treatment applications. The results suggest that InVNBL is a promising therapeutic agent, which is as good as ReDXRL, in two mouse tumor models.

The PEGylated liposomal doxorubicin improves the delivery and therapeutic efficiency of 188Re-Liposome by modulating phagocytosis in C26 murine colon carcinoma tumor model

Liposome in delivering radionuclide for cancer therapy has been expansively studied; however, liposome itself can be deliberately entrapped and destroyed by the reticuloendothelial system, causing an insufficiency of the drug delivery, which in turn would restrict the effectiveness of the drug. In this study, mice with subcutaneous implantation of C26 murine colon cancer received an experimental treatment regimen in which mice took delivery of PEGylated liposomal doxorubicin (LipoDox) first, after a three-day interval, of Rhenium-188 encapsulated into PEGylated liposome ((188)Re-Liposome) subsequently and by which suppressed the functioning of reticuloendothelial system for the short term. The data showed that based upon the biodistribution assay and the evaluation of the therapeutic efficacy, (188)Re-Liposome was more sufficiently delivered to tumor sites in mice with this treatment regimen than mice without the regimen, and that cancer mortalities in mice with the treatment regimen were much lower than the mortalities in mice without the regimen. Taken together, a new strategy proposed in this study significantly improved both the (188)Re-Liposome delivery and the effectiveness of (188)Re-Liposome, suggesting that the strategy can be an ideal treatment for cancer.

Dosimetric evaluation of nanotargeted (188)Re-liposome with the MIRDOSE3 and OLINDA/EXM programs.

ObjectiveThe OLINDA/EXM computer code was created as a replacement for the widely used MIRDOSE3 code for radiation dosimetry in nuclear medicine. A dosimetric analysis with these codes was performed to evaluate nanoliposomes as carriers of radionuclides (188Re-liposomes) in colon carcinoma-bearing mice.MethodsPharmacokinetic data for 188Re-N, N-bis (2-mercaptoethyl)-N′,N′-diethylethylenediamine (188Re-BMEDA) and 188Re-liposome were obtained for estimation of absorbed doses in normal organs. Radiation dose estimates for normal tissues were calculated using the MIRDOSE3 and OLINDA/EXM programs for a colon carcinoma solid tumor mouse model.ResultsMean absorbed doses derived from188Re-BMEDA and 188Re-liposome in normal tissues were generally similar as calculated by MIRDOSE3 and OLINDA/EXM programs. One notable exception to this was red marrow, wherein MIRDOSE3 resulted in higher absorbed doses than OLINDA/EXM (1.53- and 1.60-fold for 188Re-BMEDA and 188Re-liposome, respectively).ConclusionsMIRDOSE3 and OLINDA have very similar residence times and organ doses. Bone marrow doses were estimated by designating cortical bone rather than bone marrow as a source organ. The bone marrow doses calculated by MIRDOSE3 are higher than those by OLINDA. If the bone marrow is designated as a source organ, the doses estimated by MIRDOSE3 and OLINDA programs will be very similar.

Imaging, biodistribution and efficacy evaluation of 188Re-human serum albumin microspheres via intraarterial route in an orthotopic hepatoma model

Abstract Purpose: Liver cancer is the second most common cause of death worldwide. This study was to investigate the SPECT/CT, ultrasound, biodistribution and therapeutic evaluation of 188Re-human serum albumin microspheres (188Re-HSAM) in the GP7TB orthotopic hepatoma rat model. Materials and methods: HSAM was labeled with 188Re by using a home-made kit and microwave system. The 188Re-HSAM was administered via intraarterial route. The in vivo distribution of 188Re-HSAM was determined by biodistribution analysis and nanoSPECT/CT system. In efficacy, tumor volumes were tracked longitudinally by three-dimensional ultrasound. Results: The biodistribution and nanoSPECT/CT imaging showed that 188Re-HSAM could accumulate in liver and tumor. The correlation coefficient of tumor volumes done by three-dimensional ultrasound and at autopsy was 0.997. In efficacy, tumor volume in the normal saline-treated group was 1803.2 mm3 at 54 days after tumor inoculation. Tumor volumes in the 103.6 MBq and 240.5 MBq of 188Re-HSAM treated groups were 381 and 267.4 mm3 (p = 0.001 and 0.004), respectively. Conclusions: These results show that three-dimensional ultrasound with a high spatial resolution and contrast in soft tissue can become imaging modality in assessing tumor burden and tumor progression in an orthotopic rat model. The longitudinally therapeutic evaluation of 188Re-HSAM demonstrated dose-dependent tumor growth inhibition with increased dose in the GP7TB orthotopic hepatoma rat model.

NanoSPECT/CT imaging and biodistribution of 188 Re-HSA microspheres using new radio labeling process in a GP7TB hepatoma rats model (Imaging and Biodistribution of 188 Re-HSA microspheres)

The human serum albumin microsphere (HSA microsphere) is biodegradable and biocompatible, the SPECT/CT imaging and biodistribution of 188Re-HSA microspheres using new radio labeling process were investigated in a GP7TB hepatoma rat model. The labeling efficiency of the 188Re-HSA microspheres using new radio labeling process was about 97%. The levels of radioactivity within the liver peaked at 1 h (68.325777±1.896218 %ID/organ) and then declined slowly. With image analysis, the highest uptake in liver was 69.9±3.8 %ID/organ and 59.7±5.7 %ID/organ at 48 and 72 h after administration of 188Re-HSA microspheres via TACE. The liver uptake of 188Re-HSA microspheres was steadily maintained that to increase the radioactivity to directly give damage to tumor cells. These results showed potential benefit and advantage of 188Re-HSA microspheres via liver transarterial chemoembolization (TACE) for treatment of Hepatocellular carcinoma.

Synergistic effect of combination 188Re-liposome and Lipotecan in Huh-7 subcutaneous xenograft model

Atest apparatus with electronic control system was devised to synthesis Carbon Nanoparticles (CNP) by submerged arc discharge between two pure graphite electrodes in pure liquid paraffin oil medium. Different grades of oil viscosity are used. It was found that the resultant oil from the arc process contains carbon nanoparticles. Transmission Electron Microscope (TEM) was used to characterize the output morphology of the resultant CNP. Physical and tribological properties of the resultant oil are assessed. It was found that presence of CNP in paraffin oil resulted in reduced coefficient of friction in four-ball testing machine, raising its flash point, but reduced slightly its viscosity. This system can be improved to be applied industrially in a continuous product line with added suitable dispersant. Further work is proceeding to optimize test conditions.Methods: Twenty four immature upper permanent incisors teeth, in 6 dogs of 6 month old, were selected and divided into 2 groups. Group (A), 12 teeth for dental pulp stem cells transplantation and group (B) 12 teeth for sealing with MTA paste only. Another 12 teeth, Group (C), for isolation of the dental pulp stem cells were grouped. Apical periodontitis were induced in groups (A) and (B). After disinfection, teeth were re-entered and mixture of antibiotic paste was applied for two weeks. Dental pulp stem cells were isolated from group (C) teeth of the same dog, prepared for transplantation, mixed with growth factors and transplanted in group (A) teeth while MTA was applied for group (B) teeth. Both groups (A) and (B) teeth were monitored radiographically for periradicular healing and root wall thickening and/or lengthening.W report on the effect of Au nanoparticle deposition on the colors of virus-based colorimetric sensors consisted of selfassembled M13 bacteriophage films decorated by Au nanoparticles. We observed the effect of the localized surface plasmons in the Au nanoparticles onto the virus-based self-assembled films. Recently, virus-based colorimetric sensors have demonstrated real-time detection of biochemicals with high sensitivity, and portability (Nature Communications, 5, 3043 (2014)). Therefore, it is desirable if we can obtain colored virus films in a reliable way. However, the M13 bacteriophage-based films show some variance in their colors after assembly. This can be a problem in the mass production process of virus-based colorimetric sensors for commercial use. In this study, we fabricated a biomimetic material-based colorimetric film using M13 bacteriophage, a filamentous virus that infects only bacteria, as the building block. Then, we deposited Au nanoparticles over the colorimetric film. We observed the effect of Au nanoparticle deposition on the color and morphology of the virus films by using optical and atomic force microscopy (AFM). From these studies, we provide a method for structural color enhancement of biomimetic material-based colorimetric films.B vanadate has become most promising material for photocatalytic applications from last decade due to its visible light driven reactions in the degradation of organic pollutants. However, it is well known that doping agents may enhance the catalytic activities. In this context, investigations on nano-sized BiVO4 oxides doped by suitable metal ions are conducted in the aim to enhance the absorption in the visible spectral range and increase the efficiency of photocatalytic responses. Thus, highly crystalline silver loaded BiVO4 are prepared by mechano-chemical reaction between bismuth oxide (Bi2O3) and vanadium oxide (V2O5) in a stoichiometric ratio of 1:1 and adding metallic silver particles (<10 mm) at different atomic percentages with respect to the host oxide material (2,4,6,8 and 10%). The suitable ball milling parameters are adjusted as well as the conditions of post-synthesis annealing in order to improve the crystalline features of the samples. Complementary characterization techniques were performed to analyze the main features of the samples. Thus, XRD analysis confirmed a major high crystalline monoclinic scheelite structure for all BiVO4:Ag samples. High resolution TEM image reveals Ag presence in nano-particles along with BiVO4. The morphology of the samples investigated by FE-SEM shows particles with 50 nm sized and the effective doping by Ag ions was indeed demonstrated by (EDAX) technique. Optical absorption measurements reveal an evolution from 2.55 to 2.33 eV of BiVO4 gap with Ag doping rates.S Enhanced Raman scattering (SERS) allows detection or state identification of molecules at sub-micromolar concentrations which are especially required for accurate analysis of physiological liquids. An enormous increase of Raman signal intensity from molecules adhered on metallic nanostructures is mostly connected with plasmonic properties of metals. By today solid SERS-active substrates have attracted a great attention due to enhancement factor (EF) reproducibility and simple use. On the other hand solid substrates have to be composed of highly ordered arrays of metallic nanostructures which are fabricated by complicated and expensive nanoengineering methods. In this report, results of a research of porous silicon (PS) as a template for the fabrication of SERS-active substrates are presented. PS was formed by an electrochemical anodization of bulk silicon in HF-based solutions. Dimensions of pores and silicon crystallites in PS were varied from a couple of nanometers to micron by the anodization regimes and the type of bulk silicon. Metallic nanostructures were deposited on PSby “wet”methods. PS templates provided fabrication of different morphological forms of metallic structures (nanoparticles, dendrites, nanovoids, etc.). It was found that plasmonic properties of the metallic nanostructures strongly depend on the PS morphology and the metal deposition regimes. SERS-activity of the obtained substrates was studied using aqueous or alcoholic solutions of rhodamine6G and metallic porphyrins as analytes. It was estimated that EF of SERS-active substrate based on PS template can reach 109. Deviation of EF reproducibility from substrate to substrate was shown to be less than 20 %.W examined room temperature band-to-band tunneling in 2D InAs/3D GaSb heterostructures. Specifically, multisubband, gate-controlled negative differential resistance is observed in InAs/AlSb/GaSb junctions. Due to spatial confinement in the 10nm-thick InAs layer, tunneling contributions from two distinct subbands are observed as sharp steps in the current-voltage characteristics. It is shown that the relative position of the steps can be controlled via external gate bias. Additionally, the extracted separation in the subband energy agrees well with the calculated values. This is the first demonstration of a gate controlled tunneling diode with multiple subband contributions. By further improving the fabrication techniques, InAs/AlSb/GaSb FET is for the first time demonstrated. Device analysis indicates that Dit plays an important role on device performances and the experimental result clarifies the role of the tunneling junction width with respect to the gate width.H acid (HA) is a non-sulfated glycosaminoglycan organic polymer, found as structural component of the extracellular matrix (ECM) in mammalian bone marrow and loose connective tissues of our body. Hyaluronic acid also plays a major role in cell proliferation, motility, cell adhesion and gene expression. Cellular HA receptors such as CD44+ and RHAMM are over expressed in cancer which makes it a good candidate for tumor targeting purpose. Here we have developed a T1 gadolinium contrast agent based on Hyaluronic acid (HA) that target CD44+ receptor over expression in cirrhosis which also display higher relaxation property than primovist and better contrast–to–noise ratio (CNR) at 20 min and even at 2 hr time period. Superparamagnetic iron oxide nanoparticles (SPION) have emerged as an MRI contrast agent primarily for tumor imaging due to their efficacy and safety, proven by clinical application with a series of marketed SPION-based contrast agents. For the purpose of tumor diagnosis iron oxide nanoparticle coated with Hyaluronic acid (HA-SPION) as T2 contrast agent was synthesized with co-PEGylation strategy for increased bioavailabilty to tumor region. And finally, hyaluronic acid micelle that can encapsulate hydrophobic anti-cancer drug such as paclitaxel that specifically target CD44+ overexpressing tumor are synthesised which can act as promising drug delivery vehicle.P sulfide) (PPS) is well known for its heat resistance, high mechanical strength, excellent chemical resistance, and good electronic properties. It is used in many areas, especially in electronics, mechanical, and chemical engineering. In order to improve thermal and electrical properties of PPS as well as to expand its application, a series of PPSbased nanocomposite films containing multiwalled carbon nanotube (MWCNT) of 0.1~10.0 wt% as functional reinforcing nanofiller were manufactured by melt-mixing and -compression. The microstructures, thermal and electrical properties of the nanocomposite films were investigated as a function of the MWCNT content. FT-IR spectra and SEM images confirmed that PPS/MWCNT nanocomposite films supported that MWCNTs were randomly dispersed in the PPS matrix. DSC and TGA data indicated that the thermal transition temperatures as well as the degradation temperatures of the nanocomposite films were influenced by the presence of the MWCNT. The electrical resistivity of the nanocomposite films were dramatically changed with increasing the MWCNT by exhibiting a typical percolation threshold. Furthermore, the applications of PPS/MWCNT nanocomposite films as electric heating elements were demonstrated. The electric heating performance of the nanocomposite films with high MWCNT contents was systematically characterized in terms of temperature response rapidity, saturated maximum temperature, and electric power efficiency and operational stability at applied voltages up to 100V.G Quantum Dots (GQDs) are proving to be effective imaging paraphernalia for the comprehension of morphological alterations in the cellular membrane due to high absorption coefficients and quantum efficiency. Such quantum dots can be used in drug/delivery vehicles, biolabelling as well as in PCR. An upsurge of expanded interest in the field of magnetic nanotechnology has led us to allow indepth exploitation of magnetic nanoparticles in nanomedicine. Encapsulating the core made up of magnetic nanoparticles by Gold nanoshell leads to the development of a proficient biocompatible and stabilized drug/delivery system under physiological conditions. Further a nanocomposite was created by allowing conglomeration of AuFe3O4 core-shell with GQDs. This modular design enables Au-Fe3O4-GQDs to perform multiple functions simultaneously, such as in multimodal imaging, drug delivery and real-time monitoring, as well as combined therapeutic approaches. The ability of MNPs to enhance proton relaxation of specific tissues and serve as MR imaging contrast agents is one of the most promising applications of nanomedicine. In the present work, Au-Fe3O4 nanoparticles are used as able cargo for the docking of anti-cancer drug such as Doxorubicin (DOX) using cysteamine as a linker for the attachment. The attachment could be monitored using UV-visible spectroscopy. The stability of Au-Fe3O4 nanoparticles was scrutinized by measuring the flocculation parameter which was found to be in the range of 0-0.65. Further, zeta potential measurements confirmed the pH of 7.4 at which maximum drug attachment can take place. The amalgamation of the drug along with activated folic acid as a navigational molecule is the critical phase for targeted drug delivery. Attachments were verified using FTIR and NMR which confirmed the formation of non-covalent interactions. The drug loading capacity of the Au-Fe3O4 was found to be 76%. Drug-release was studied using the AC magnetic field generator and was found to be temperature dependent phenomena. GQDs were found to be effective players in tracking the drug-delivery vehicle around the miscreant cell and inside them. Au-Fe3O4-GQD-FA-DOX complex was found to be comparatively non-toxic for normal cells and considerably toxic for Hep-2 cells due to hyperthermal properties of SPIONS and targeted-mechanism of folic acid.S is severe chronic disabling brain disease affecting about 24 million people worldwide and 4 million people in India as WHO 2011 report. Asenapine maleate (ASN) is a novel psychopharmacologic agent recommended for treatment of Schizophrenia and Bipolar disorder. ASN suffers with the problems of poor aqueous solubility, very low oral bioavailability (1-2%) and high patient non-adherence. Therefore, objective of the present study was to prepare Nanostructured Lipid Carriers (NLCs) of Asenapine maleate to improve the bioavailability and enhance the uptake of ASN to the brain via intranasal route. Asenapine loaded NLCs (ASN-NLCs) were prepared by melt emulsification-high shear homogenization method. For preparation of NLCs, Glyceryl monostearate, Oleic acid and Tween 80 were used as solid lipid, liquid lipid and surfactant, respectively. ASN-NLCs were characterized for particle size, zeta potential, entrapment efficiency, in-vitro drug release study, XRD and DSC. Stability study was performed at 25°C/60% RH for three months. Further, pharmacodynamic studies (paw test and l-dopa induced locomotor activity test) were performed on rat model to evaluate the efficacy of formulation. ASNNLCs were successfully prepared and optimized with particle size below 200 nm, zeta potential -15.38±2.17 mV, EE 82±3.5% and more than 85% drug release in 24 h. The XRD and DSC analysis indicate that Asenapine was present in amorphous state in NLCs. The ASN-NLCs were stable over 3 month studies. In pharmacodynamic studies, significant increase (p<0.05) in antipsychotic potential was observed in ANS-NLCs as compared to pure drug. These results indicate that the NLCs are having a potential to deliver drug into the brain from the non-invasive intranasal route.P is extremely abundant in the earth’s crust and distributed very widely. Due to the particularity of it, pyrite is an important research subject in several different fields such as gold prospecting, metallogenic environment, metallogenic prediction, and even functional material. Studies have shown that different Fe/S atom ratio, impurity, and temperature, could all cause crystal defects in the crystal interior, which could lead to the occurrence of crystal lattice structure distortion, which then could affect the thermoelectricity of pyrite. Thus, there might exist a response relationship between the mineral crystal structure and thermoelectricity. However, presently, the research on the relation between the response researches is still rare. In this paper, the samples were obtained by thermal sulfidation during 320~420°C and studied using a SEM ,a XRD and thermoelectricity instrument respectively, to study the crystal morphology, structure and thermoelectricity. The research shows that:(1) Pyrite prepared by thermal sulfidation, are p-type with a small scope of thermoelectric coefficient and good stability. (2) The value of the thermoelectric coefficient was correlated with the growth degree of crystal planes, the higher degree of crystallinity, the higher thermoelectric coefficient. (3) There exists a significantly different influence from different directions on the thermoelectric coefficient; the thermoelectric coefficient of low-index surface (111), (200) and (210) was significantly greater than high-index surface (220) and (311). (4) In the pyrite crystal, the different reticular density caused different thermoelectric. The greater the reticular density, the greater is the influence on the thermoelectric coefficient.