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We demonstrate that several visible-light mediated carbon–heteroatom cross-couplings can be carried out using a photoactive NiII precatalyst that forms in situ from a nickel salt and a bipyridine ligand decorated with two carbazole groups (Ni(Czbpy)Cl2). The activation of this precatalyst towards cross-couplings follows a hitherto undisclosed mechanism that is different from previously reported light-responsive nickel complexes that were reported to undergo metal-to-ligand charge transfer. Theoretic and spectroscopic investigations revealed that irradiation of Ni(Czbpy)Cl2 with visible-light causes an initial intraligand charge transfer event that triggers productive catalysis. Ligand polymerization affords a porous, recyclable organic polymer for heterogeneous nickel catalysis of cross-couplings. The heterogeneous catalyst shows stable performance in a packed-bed flow reactor during a week of continuous operation.

Zwitterionic hydrogels have promising potential as a result of their anti-fouling and biocompatible properties, but they have recently also gained further attention due to their controllable stimuli responses. We successfully synthesized two zwitterionic polymers, poly(2-methacryloyloxyethyl phosphorylcholine) (poly-MPC) and poly(2-(methacryloyloxy)ethyl dimethyl-(3-sulfopropyl)ammonium hydroxide) (poly-DMAPS), which have complementary ionic sequences in their respective zwitterionic side groups and likely form an interpenetrating double network to improve their mechanical strength. The synthesized poly-MPC was blended in a poly-DMAPS matrix (MD gel) and showed high viscosity, while poly-DMAPS was blended in a poly-MPC hydrogel (DM gel) and revealed UCST behavior as the temperature increased. In addition, cross-section images of the MD hydrogel exhibited its compact and uniform structure, while the DM gel was found to exhibit a porous micro-structure with clear boundaries. The results explained the low viscosity of the DM gel, which was also confirmed via 3D Raman mapping. To sum up, the preliminary data demonstrated that binary zwitterionic hydrogels have thermosensitive mechanical properties, promoting further bio-applications in the future, such as in wound healing.

Integrating anticancer drugs and diagnostic agents in a polymer nanosystem is an emerging and promising strategy for improving cancer treatment. However, the development of multifunctional nanoparticles (NPs) for an "all-in-one" platform characterized by specific targeting, therapeutic efficiency, and imaging feedback remains an unmet clinical need. In this study, pH-responsive mixed-lanthanide-based multifunctional NPs were fabricated based on simple metal-ligand interactions for simultaneous cancer cell imaging and drug delivery. We investigated two new systems of alginate-polydopamine complexed with either terbium/europium or dysprosium/erbium oxide NPs (Tb/Eu@AlgPDA or Dy/Er@AlgPDA NPs). Tb/Eu@AlgPDA NPs were then functionalized with the tumor-targeting ligand folic acid (FA) and loaded with the anticancer drug doxorubicin (DOX) to form FA-Tb/Eu@AlgPDA-DOX NPs. Using such systems, the mussel-inspired property of PDA was introduced to improve tumor targetability and penetration, in addition to active targeting (via FA-folate receptor interactions). Determining the photoluminescence efficiency showed that the Tb/Eu@AlgPDA system was superior to the Dy/Er@AlgPDA system, presenting intense and sharp emission peaks on the fluorescence spectra. In addition, compared to Dy/Er@AlgPDA NPs (82.4%), Tb/Eu@AlgPDA NPs exhibited negligible cytotoxicity with93.3% HeLa cell viability found in MTT assays at NP concentrations of up to 0.50 mg/mL and high biocompatibility when incubated with zebrafish (

Biotin receptors are overexpressed by various types of solid cancer cells and play a significant role in tumor metabolism, growth, and metastasis. Thus, targeting the biotin receptors on tumor cells may enhance the efficiency and reduce the side-effects of chemotherapy. The aim of this study was to develop a biotin-coupled poly(amido)amine (PAMAM) (PG4.5) dendrimer nanoparticle to enhance the tumor-specific delivery and intracellular uptake of anticancer drugs via receptor-mediated endocytosis. We modified PG4.5 with diethylenetriamine (DETA) followed by biotin via an amide bond and characterized the resulting PG4.5-DETA-biotin nanoparticles by 1H NMR, FTIR, and Raman spectroscopy. Loading and releasing of gemcitabine (GEM) from PG4.5-DETA-biotin were evaluated by UV&ndash, Visible spectrophotometry. Cell viability and cellular uptake were examined by MTT assay and flow cytometry to assess the biocompatibility, cellular internalization efficiency and antiproliferative activity of PG4.5-DETA-biotin/GEM. Gemcitabine-loaded PG4.5-DETA-biotin nanoparticles were spherical with a particle size of 81.6 &plusmn, 6.08 nm and zeta potential of 0.47 &plusmn, 1.25 mV. Maximum drug-loading content and encapsulation efficiency were 10.84 &plusmn, 0.16% and 47.01 &plusmn, 0.71%, respectively. Nearly 60.54 &plusmn, 1.99% and 73.96 &plusmn, 1.14% of gemcitabine was released from PG4.5-DETA-biotin/GEM nanoparticles after 48 h at the acidic pH values of 6.5 and 5, respectively. Flow cytometry and fluorescence microscopy of cellular uptake results revealed PG4.5-DETA-biotin/GEM nanoparticles selectively targeted cancer cells in vitro. Cytotoxicity assays demonstrated gemcitabine-loaded PG4.5-DETA-biotin significantly reduced cell viability and induced apoptosis in HeLa cells. Thus, biotin-coupled PG4.5-DETA nanocarrier could provide an effective, targeted drug delivery system and selectively convey gemcitabine into tumor cells.

This is the peer reviewed version of the following article: Hsu, W‐H., Csaba, N., Alexander, C., Garcia‐Fuentes, M. (2020), Polyphosphazenes for the delivery of biopharmaceuticals. J Appl Polym Sci, 137, 48688. doi: https://doi.org/10.1002/app.48688, which has been published in final form at https://doi.org/10.1002/app.48688. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions Polyphosphazenes (PPZs) are a relatively new family of polymers based on a nitrogen- phosphorous backbone where organic side-groups can be grafted. The synthetic route to PPZs is highly versatile such that it is possible to add many different functionalities that change completely the physicochemical and biological properties of the polymers. For instance, PPZs can be designed with a variety of organic side groups that render these materials biodegradable and highly biocompatible. Based on these positive features, PPZs have been explored for many biomedical applications including the design of numerous advanced drug delivery systems. In this area, PPZs have been particularly investigated as materials for the formulation of biopharmaceuticals of high added value. These include protein- and polynucleotide-based medicines, applications where PPZ carriers have obtained very positive results in pre-clinical models. A further area of major interest for PPZs has been vaccination, where these materials have obtained excellent results in vivo as polymer adjuvants and have advanced to clinical evaluation. This work has been funded by Ministerio de Economía y Competitividad (MINECO-RETOS, Grant MAT2017-84361-R, Feder Funds) and Xunta de Galicia (Grupos de Referencia Competitiva, Feder Funds) to MGF and Engineering and Physical Sciences Research Council Grants EP/N006615/1, EP/ N03371X/1 to CA. WHH was a recipient of a contract from EU Erasmus Mundus NanoFar joint doctorate program SI

Successful gene therapies rely on methods that safely introduce DNA into target cells and enable subsequent expression of proteins. To that end, peptides are an attractive materials platform for DNA delivery, facilitating condensation into nanoparticles, delivery into cells, and subcellular release to enable protein expression. Peptides are programmable materials that can be designed to address biocompatibility, stability, and subcellular barriers that limit efficiency of non-viral gene delivery systems. This review focuses on fundamental structure-function relationships regarding peptide design and their impact on nanoparticle physical properties, biologic activity, and biocompatibility. Recent peptide technologies utilize multi-dimensional structures, non-natural chemistries, and combinations of peptides with lipids to achieve desired properties and efficient transfection. Advances in DNA cargo design are also presented to highlight further opportunities for peptide-based gene delivery. Modern DNA designs enable prolonged expression compared to traditional plasmids, providing an additional component that can be synergized with peptide carriers for improved transfection. Peptide transfection systems are poised to become a flexible and efficient platform incorporating new chemistries, functionalities, and improved DNA cargos to usher in a new era of gene therapy.

The recent discovery of small interfering RNAs (siRNAs) has opened new avenues for designing personalized treatment options for various diseases. However, the therapeutic application of siRNAs has been confronted with many challenges because of short half-life in circulation, poor membrane penetration, difficulty in escaping from endosomes, and insufficient release into the cytosol. To overcome these challenges, we designed a diethylenetriamine (DETA)- and tetraethylenepentamine (TEPA)-modified polyamidoamine dendrimer generation 4.5 (PDG4.5), and characterized it using 1H nuclear magnetic resonance (NMR), 13C NMR, correlation spectroscopy (COSY), heteronuclear single-quantum correlation spectroscopy (HSQC), and Fourier transform infrared (FTIR) spectroscopy followed by conjugation with siRNA. The PDG4.5-DETA and PDG4.5-TEPA polyplexes exhibited spherical nanosize, ideal zeta potential, and effective siRNA binding ability, protected the siRNA from nuclease attack, and revealed less cytotoxicity of PDG4.5-DETA and PDG4.5-TEPA in HeLa cells. More importantly, the polyplexes also revealed good cellular internalization and facilitated translocation of the siRNA into the cytosol. Thus, PDG4.5-DETA and PDG4.5-TEPA can act as potential siRNA carriers in future medical and pharmaceutical applications.

In a malignant tumor, overexpression of pro-angiogenic factors like vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks characterized by leaky, chaotically organized, immature, thin-walled, and ill-perfused. As a result, hostile tumor environment would be developed and profoundly hinders anti-cancer drug activities and fuels tumor progression. In this study, we develop a strategy of sequential sustain release of anti-angiogenic drug, Bevacizumab (BVZ), and anti-cancer drug, Doxorubicin (DOX), using poly ( d , l -Lactide)- Poly (ethylene glycol) -Poly ( d , l -Lactide) (PDLLA-PEG-PDLLA) hydrogel as a local delivery system. The release profiles of the drugs from the hydrogel were investigated in vitro which confirmed that relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) at pH 6.5 for prolonged period. The in vitro cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml−1 concentration on HaCaT and HeLa cells. Likeways, the in vitro degradation of the copolymer showed 41.63 ± 2.62% and 73.25 ± 4.36% weight loss within 6 weeks at pH 7.4 and 6.5, respectively. After a single intratumoral injection of the drug-encapsulated hydrogel on Hela xenograft nude, hydrogel co-loaded with BVZ and Dox displayed the highest tumor suppression efficacy for up to 36 days with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drug by hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

This is the peer reviewed version of the following article: Hsu, W.‐H., Sánchez‐Gómez, P., Gomez‐Ibarlucea, E., Ivanov, D.P., Rahman, R., Grabowska, A.M., Csaba, N., Alexander, C. and Garcia‐Fuentes, M. (2019), Structure‐Optimized Interpolymer Polyphosphazene Complexes for Effective Gene Delivery against Glioblastoma. Adv. Therap., 2: 1800126. doi:10.1002/adtp.201800126, which has been published in final form at https://doi.org/10.1002/adtp.201800126. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions Safe and efficient gene delivery vectors would enhance the prospects for polynucleotide-based therapies. Herein we describe a new approach towards structurally-optimized gene vector design based on the preparation of clickable poly(allylamino-phosphazene)s that can be converted to several cationic and anionic derivatives via thiol-ene addition. Simultaneous co-incubation of alkylamine- and alkylcarboxylate-poly(phosphazenes) with polynucleotides generated binary-polyelectrolyte nanoparticles. Screening of a series of these complexes for transfection in glioblastoma cells showed that the inclusion of 6-mercaptohexanoic acid substituted poly(phosphazene)s in the complexes resulted in 6-fold and 19-fold higher luciferase expression in U87MG cells and primary GBM1 cell- line, respectively. This effect was attributed to the specific ionization properties of this materials that improved polyplex intracellular trafficking. Transfection in 3D-spheroid models and subcutaneous xenograft U87MG tumors confirmed higher transgene expression for the binary cationic/anionic poly(phosphazene) complexes compared to the related polycation-pDNA complexes and to PEI- pDNA complexes. The data also indicated a notable capacity of the mixed complexes to deliver genes to the inner cores of tumor spheroids. Extension of this approach to siRNA delivery showed that the mixed poly(phosphazene) complexes were able to silence DYRK1A, a gene implicated in tumor initiation and progression, reducing U87MG cell renewal in vitro and delaying tumor growth in vivo. This work has been funded by Ministerio de Economía y Competitividad (MINECO-RETOS, Grant MAT2017-84361-R, Feder Funds) and Xunta de Galicia (Grupos de Referencia Competitiva, Feder Funds) to MGF and Engineering and Physical Sciences Research Council Grants EP/N006615/1, EP/ N03371X/1 to CA. WHH was a recipient of a contract from EU Erasmus Mundus NanoFar joint doctorate program SI

The tricyclohexylphosphine-catalyzed [3 + 2] cycloaddition of (E)-alkyl 5-substituted phenylpent-4-en-2-ynoates with [60]fullerene was studied. This reaction undergoes an initial 1,3-addition of phosphines toward the α-carbons of enynoates. Subsequent cycloaddition of the generated 1,3-dipoles with [60]fullerene and elimination of tricyclohexylphosphines resulted in cyclopentenofullerenes in 20-43% yields. The isolated cyclopentenofullerenes were observed to serve as n-type materials in organic photovoltaics, providing a maximum average power conversion efficiency of 3.79 ± 0.29% upon embedding with P3HT in the active layer.

Obesity and type 2 diabetes have become serious health problems in 21st century. Development of non-invasive treatment to treat obesity and type-2 diabetes is still unmet needs. For targeting on this, one of the promising treatments is to implant an intestine sleeve in the gastrointestinal tract for limitation of food absorption. In this context, biodegradable polymer intestine sleeve was composed of polycaprolactone (PCL), poly-DL-lactic acid (PDLLA) and disk-shape nano-clay (Laponite®), and fabricated as an implantable device. Here, Laponite® as a rheological additive to improve the compatibility of PCL and PDLLA, and the polymers/clay composites were also evaluated by scanning electron microscopy SEM analysis and mechanical measurements. The mass ratio 90/10/1 of PCL/PDLLA/Laponite® composite was selected for fabrication of intestine sleeve, because of the highest toughness and flexibility, which are tensile strength of 91.9 N/mm2 and tensile strain of 448% at the failure point. The prepared intestine sleeve was implanted and deployed at the duodenum in type2 diabetic rats, providing significant benefits in control of the body weight and blood glucose, while compared with the non-implanted type 2 diabetic rats. More importantly, the food intake records and histopathological section reports presented that the implanted rats still have normal appetites and no noticeable acute symptoms of inflammation in the end of the test. These appreciable performances suggested the implantation of biocompatible polymer composites has a highly potential treatment for obesity and type 2 diabetes.

Metastasis is a pathogenic spread of cancer cells from the primary site to surrounding tissues and distant organs, making it one of the primary challenges for effective cancer treatment and the major cause of cancer mortality. Heparin-based biomaterials exhibit significant inhibition of cancer cell metastasis. In this study, a non-anticoagulate heparin prodrug is developed for metastasis treatment with a localized treatment system using temperature sensitive, injectable, and biodegradable (poly-(e-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(e-caprolactone-co-lactide) polymeric hydrogel. The drug molecule (heparin) is conjugated with the polymer via esterification, and its sustained release is ensured by hydrolysis and polymeric biodegradation. An aqueous solution of the polymer could be used as an injectable solution at below 25 °C and it achieves gel formation at 37 °C. The anti-metastasis effect of the hydrogels is investigated both in vitro and in vivo. The results demonstrated that local administration of injectable heparin-loaded hydrogels effectively promote an inhibitory effect on cancer metastasis.

Redox-responsive diselenide bond containing triblock copolymer Bi(mPEG-SeSe)-PCL,Bi(mPEG-SeSe)-PCL was developed for specific drug release in cancer cells. Initially, ditosylated polycaprolactone was prepared via the reaction between polycaprolactone diol (PCL-diol) and tosyl chloride (TsCl). Next, Bi(mPEG-SeSe)-PCL was synthesized via the reaction between ditosylated polycaprolactone and sodium diselenide initiated poly (ethylene glycol) methyl ether tosylate. The synthesized amphiphilic triblock copolymer could self-assemble into uniform nanoparticles in aqueous medium and disassemble upon redox stimuli. The Bi(mPEG-SeSe)-PCL nanoparticles showed a DOX loading content of 5.1 wt% and a loading efficiency of 49%. In vitro drug release studies showed that about 62.4% and 56% of DOX was released from the nanoparticles during 72 h at 37 °C in PBS containing 2 mg/mL (6 mM) GSH and 0.1% H2O2, respectively, whereas only about 30% of DOX was released in PBS under the same conditions. The cell viability (MTT assays) results showed that the synthesized material was biocompatible with above 90% cell viability, and that the DOX-loaded Bi(mPEG-SeSe)-PCL nanoparticles had a high antitumor activity against HeLa cells and low antitumor activity against HaCaT cells, following a 24-h incubation period. Three-dimensional (3D) spheroids of HeLa cells were established for the evaluation of localization of the DOX-loaded nanoparticles into spheroids cells and the successfully inhibition of 3D tumor spheroid growth. The results indicated that the synthesized material Bi(mPEG–SeSe)-PCL was biocompatible and it could be a potential candidate for anticancer drug delivery system.

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.

Rhenium-188 (188Re) displays abundant intermediate energy β emission and possesses a physical half-life of 16.9 h. Sorafenib is an orally available multikinase inhibitor that targets Raf kinases and vascular endothelial growth factor receptors (VEGFRs). Sorafenib has demonstrated preclinical and clinical activity against several types of tumors, such as renal cell and colorectal carcinoma. In this study, we investigated the efficacy of radiotherapeutics of 188Re-liposomes combined with sorafenib in a C26-luc metastatic colorectal liver tumour mouse model. Liver metastases were established by intrasplenic injection of C26-luc murine colon cancer cells. Based on the results of the toxicity assessment, an administration dose of 80% the maximum tolerated dose was selected. 188Re-liposomes were administered on day 1, when metastases of several hundred micrometers in diameter were observed. In the combination therapy group, 10 mg/kg sorafenib (co-developed and co-marketed by Bayer and Onyx Pharmaceuticals as Nexavar) was administered every other day for 1 week and the survival of mice was assessed. The tumor growth was more significantly inhibited in the 188Re-liposome plus sorafenib group compared with the 188Re-liposome alone, sorafenib alone and untreated normal saline groups (P=0.0000). Furthermore, 188Re-liposomes combined with sorafenib achieved higher survival rates compared with the 188Re-liposome alone, sorafenib alone and untreated normal saline groups (P=0.0000). These results support the use of combined radio-chemotherapy with 188Re-liposomes plus sorafenib as a viable treatment option in the adjuvant setting for liver metastases of colorectal cancer.

Although the structural equation modeling (SEM) methodology is a powerful tool for validating psychological measurements, few studies have used complete SEM-based indexes in test validation. This study developed and validated the cyberspace positive psychology scale (C-PPS) via SEM techniques. A total of 411 college students were recruited from four universities in Taiwan for the study. Hierarchical confirmatory factor analysis was used to test construct validity, and a structural model provided criterion-related validity. Reliability was reported via composite reliability. Results of the analyses show that the C-PPS demonstrated high reliability and good construct validity. Furthermore, criterion-related validity identified that although positive psychology in cyberspace and positive psychology in real life contexts are correlated, the two are also distinguishable. To conclude, the C-PPS is valid and reliable. The validation of the C-PPS indicates that college students can exhibit positive psychological traits in both the real and virtual worlds.

The sterically polymer-based liposomal complexes (SPLexes) were formed by cationic polymeric liposomes and pH-sensitive diblock copolymer were studied for their capabilities in improving the stability with high efficiency of siRNA delivery. The SPLexes were formed a dual-shelled structure and uniform size distribution. The PEGylated outer shell could mitigate the phagocytosis and reduce the cytotoxicity. Moreover, the folated SPLexes improved 42.9× accumulation in vitro and 1.7× tumor uptake in vivo in contrast with nonfolated SPLexes. The protonated copolymer at low pH would improve the siRNA released into cytoplasm following SPLexes fusion with the endo/lysosome membrane and inhibited the protein expression to 75.6 ± 4.5% efficiently. Results of this study significantly contribute to efforts to develop lipoplexes based siRNA delivery systems.

This study investigates the psychometric properties of Chinese-version short-form 10-item CES-D (i.e., CESD-10) in clinical depression patients and non-clinical college students by structural equation modeling approach. Several statistical procedures are applied to investigate the psychometric properties of CESD-10. First, the single factor model of CESD-10 shows merely mediocre fit due to “error term correlations”. The two pairs of error term correlations indicate that CESD-10 has redundant items and negative-worded effect. The revised model, based on the modification index, demonstrates good fit, and is adopted for subsequent analysis. Results of the SEM-based method show that configure invariance holds, while weak factorial invariance is not supported. A comparison the psychometric properties of the two groups shows that the clinical sample has better reliability, while the non-clinical sample has superior factorial validity. This finding confirms that the Chinese-version CESD-10 is most appropriate for the nonclinical, general population, although it is also valid for the clinically depressed.

Camouflage images contain one or more hidden figures that remain imperceptible or unnoticed for a while. In one possible explanation, the ability to delay the perception of the hidden figures is attributed to the theory that human perception works in two main phases: feature search and conjunction search. Effective camouflage images make feature based recognition difficult, and thus force the recognition process to employ conjunction search, which takes considerable effort and time. In this paper, we present a technique for creating camouflage images. To foil the feature search, we remove the original subtle texture details of the hidden figures and replace them by that of the surrounding apparent image. To leave an appropriate degree of clues for the conjunction search, we compute and assign new tones to regions in the embedded figures by performing an optimization between two conflicting terms, which we call immersion and standout , corresponding to hiding and leaving clues, respectively. We show a large number of camouflage images generated by our technique, with or without user guidance. We have tested the quality of the images in an extensive user study, showing a good control of the difficulty levels.

Rhenium-188 (188Re) displays abundant intermediate energy β emission and possesses a physical half-life of 16.9 h. Sorafenib is an orally available multikinase inhibitor that targets Raf kinases and vascular endothelial growth factor receptors (VEGFRs). Sorafenib has demonstrated preclinical and clinical activity against several types of tumors, such as renal cell and colorectal carcinoma. In this study, we investigated the efficacy of radiotherapeutics of 188Re-liposomes combined with sorafenib in a C26-luc metastatic colorectal liver tumour mouse model. Liver metastases were established by intrasplenic injection of C26-luc murine colon cancer cells. Based on the results of the toxicity assessment, an administration dose of 80% the maximum tolerated dose was selected. 188Re-liposomes were administered on day 1, when metastases of several hundred micrometers in diameter were observed. In the combination therapy group, 10 mg/kg sorafenib (co-developed and co-marketed by Bayer and Onyx Pharmaceuticals as Nexavar) was administered every other day for 1 week and the survival of mice was assessed. The tumor growth was more significantly inhibited in the 188Re-liposome plus sorafenib group compared with the 188Re-liposome alone, sorafenib alone and untreated normal saline groups (P=0.0000). Furthermore, 188Re-liposomes combined with sorafenib achieved higher survival rates compared with the 188Re-liposome alone, sorafenib alone and untreated normal saline groups (P=0.0000). These results support the use of combined radio-chemotherapy with 188Re-liposomes plus sorafenib as a viable treatment option in the adjuvant setting for liver metastases of colorectal cancer.

The aim of this study was to investigate the correlation between Facebook involvement and internet addiction. We sampled 577 university students in Taiwan and administered a survey of Facebook usage, Facebook involvement scale (FIS), and internet addiction scale. The FIS comprises three factors (salience, emotional support, and amusement). Results showed that the Facebook involvement scale had good reliability and validity. The correlation between Facebook involvement and internet addiction was measured at .395. This means that a higher degree of Facebook involvement indicates a greater degree of psychological dependency on the internet, and a greater propensity towards social withdrawal and other negative psychological consequences associated with internet addiction. Besides, the correlations between three factors of FIS (salience, emotional support, and amusement) and internet addiction ranged from .313-372, indicating that these neither of these factors (salience, emotional support, and amusement) is more effective than the others in predicting internet dependency., {"references":["N. B. Ellison, C. Steinfield, and Lampe, C. \"The benefits of Facebook\n\"friends:\" Social capital and college students' use of online social network\nsites.\" Journal of Computer-Mediated Communication, vol 12\n,pp.1143-1168, 2007.","F. K. Hew,\" Students- and teachers- use of Facebook\". Computers in\nHuman Behavior, vol 27(2),pp 662-676, 2011.","C. Steinfield, N. Ellison, and C. Lampe, \"Social capital, self-esteem, and\nuse of online social network sites: A longitudinal analysis\". Journal of\nApplied Developmental Psychology, vol 29, pp.434-445, 2008.","T. A., Pempek, Y. A. Yermolayeva, , and S. L. Calvert, \"College students'\nsocial networking experiences on Facebook\". Journal of Applied\nDevelopmental Psychology,vol 30(3), pp.227-238, 2009.","K. S. Young, Pathological Internet Use:\" A case that breaks the\nstereotype.\" Psychological Reports, vol 79, pp.899-902, 1996","M. Griffiths, (1998), \"Internet addiction: Does it really exist?\" In\nPsychology and the internet: Intrapersonal, interpersonal and\ntranspersonal, J. Gackenbach (Ed.), New\nYork: Academic Press, 1998, pp. 61-75.","P. Sheldon, \"The relationship between unwillingness-to-communicate\nand students- facebook use.\" Journal of Media Psychology, vol 20(2), pp.\n67-75, 2008.","R. B. Kline, , \"Principles and Practice of Structural Equation Modeling\".\nNew York: The Guilford Press, 2005.","S. C. Yu, and M, M. Yu,\" Comparison of Internet-Based and Paper-Based\nQuestionnaires in Taiwan Using Multi-Sample Invariance Approach.\"\nCyberPsychology and Behavior, vol10, pp.501-507, 2007."]}

Target geometry for mitigating phagocytosis has garnered considerable attention recently in the drug delivery field. This study examined nanoparticles (NPs) with same volume but different shapes, namely, spherical NPs (SNPs) and hexagonal nanoprisms (HNPs), and analyzed their behaviors in vitro and in vivo. These NPs were constructed with a multifunctional block copolymer component, mPEG-b-P(HEMA-co-histidine-PLA). Geometry of SNPs and HNPs was controlled by adjusting copolymer properties and particle size was controlled by adjusting formulation parameters. Nanoparticle morphology had no effect in mitigating phagocytosis when NP size was 70 nm; however, morphology had a significant effect when NP size was 120 nm. The radioactivity–time curves for 99mTc-labeled NPs, fitted by the two-compartment pharmacokinetic model, show that the prolonged plasma distribution half-life of HNPs is indicative in the bloodstream. The in vitro and in vivo studies reveal that dual stealth characteristics, pegylation and hexagonal prism structure, of nanocarriers can be adopted in clinical application for safe and efficient delivery of cancer therapy.

Feng-Yun J Huang,1 Te-Wei Lee,2 Chih-Hsien Chang,2 Liang-Cheng Chen,2 Wei-Hsin Hsu,2 Chien-Wen Chang,1 Jem-Mau Lo1 1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan; 2Institute of Nuclear Energy Research, Longtan, Taiwan Purpose: In this study, the 188Re-labeled PEGylated nanoliposome (188Re-liposome) was prepared and evaluated as a therapeutic agent for glioma.Materials and methods: The reporter cell line, F98luc was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of 188Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered 188Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the 188Re-liposome-treated rats.Results: By using bioluminescent imaging, the well-established reporter cell line (F98luc) showed a high relationship between cell number and its bioluminescent intensity (R2=0.99) in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of 188Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the 188Re-liposome-treated group than the control group (P

Parathyroid carcinoma accounts for 0.5 to 4.0% of cases of primary hyperparathyroidism. The prognosis depends largely on the extent of successful resection at the time of initial operation. Therefore, early diagnosis before surgery is important. We report 3 cases of primary hyperparathyroidism. The first patient, a 20-year-old uremic female, had refractory hypercalcemia after 5 years of hemodialysis treatment. Hypercalcemia persisted despite repeated parathyroidectomy. Pathology revealed diffuse hyperplasia of the parathyroid glands with focal adenomatous changes. Multiple pulmonary metastases were found later. The second patient, a 45-year-old female with history of nephrolithiasis, presented with severe osteoporosis. She underwent repeated parathyroidectomy for local recurrence. Pathology disclosed typical features of parathyroid carcinoma with adjacent lymph node metastasis. The third patient, a 34-year-old male, had recurrent episodes of extremity fracture and hypercalcemia with palpable neck mass. He underwent resection of the parathyroid tumor. Vascular and capsular invasions were noted microscopically. All three patients were relatively young and had extremely high intact parathyroid hormone (iPTH) level (15 to 31 times the upper limit of normal). The first patient died of hypercalcemia and respiratory failure and the other 2 were treated successfully with surgical excision and, in case 2, combined chemotherapy and radiotherapy. The latter 2 patients had no recurrence during 18 months and 14 months of follow-up, respectively. Our experience with these cases suggests that the combination of the following characteristics are highly suggestive of parathyroid carcinoma: young age, palpable neck mass, concomitant renal and skeletal disease, and extremely high iPTH level in patients with PTH-dependent hypercalcemia.