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      1. Author :
        Vijayan, Vineeth M.; Shenoy, Sachin J.; Muthu, Jayabalalan
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Materials Science and Engineering: C
      6. Products :
      7. Volume :
        76
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Theranostics; Bioimaging; Octreotide-conjugation; Fluorescent PEGylated nanogel; IVIS; IVIS FLI in vivo
      12. Abstract :
        Targeted nanocarriers can significantly increase the efficiency of therapeutic formulations by ensuring the site specific delivery of the cargo. Here in, we report a novel actively targeted fluorescent nanogel, PMB-OctN, based on photoluminescent comacromer [PEG-maleic acid-4 aminobenzoic acid], diethylene glycoldimethacrylate and octreotide. The nanogel has spherical morphology with average particle size around 40nm. The PMB-OctN can load 78% of anticancer drug and release for 5days and beyond in a sustained way. The studies on drug delivery of doxorubicin from PMB-OctN carried out with cervical cancer cells. Hela revealed appreciable therapeutic capability. The studies on cellular uptake of the nanogel revealed increased cellular uptake when compared to the nontargeted nanogel. The study on fluorescence bioimaging of the PMB-OctN in mice has demonstrated near-IR imaging capability. Then biodistribution studies of the PMB-OctN in mice have also revealed longer in vivo circulation lifetime. Taken together, these results suggest that the synthesized actively targeted nanogel, PMB-OctN stands as a promising candidate for theranostic applications. As octreotide based therapeutic formulation are already used in clinics, this newly reported strategy of near-IR fluorescence labeling of octreotide has important clinical relevance.
      13. URL :
        http://www.sciencedirect.com/science/article/pii/S0928493116325346
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13545
      15. Serial :
        13674
      1. Author :
        Verwilst, Peter; Han, Jiyou; Lee, Jiyeong; Mun, Sora; Kang, Hee-Gyoo; Kim, Jong Seung
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        115
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Theranostics; Azobenzene; Hypoxia; Cancer; Drug targeting; Maestro
      12. Abstract :
        An azobenzene scaffold serves as both a fluorescence quencher and nitrogen mustard deactivator in a mitochondrial targeting unit bearing theranostic drug delivery system (DDS). The DDS exhibited a tissue selectivity for tumors with aggressive phenotypes, and the efficient in vitro and in vivo azoreduction under hypoxia conditions resulted in bright fluorescence at the tumor site as well as the in situ activation of the prodrug. In vivo therapeutic experiments demonstrated a significant reduction in tumor growth versus number of controls and ex vivo tissue analysis confirmed tissue normalization with strongly reduced angiogenic markers and suppressed cell proliferation. Mechanistic insight of the DDS's mode of action was gained by gene and protein expression experiments, aided by a proteomic analysis, revealing the circumvention of cellular drug resistance pathways as well as the normalization of Slit-Robo signaling, and the involvement of granzyme-triggered mitochondria-mediated apoptosis. Overall, the combined high sensitivity and synthetic ease as well as excellent therapeutic response suggests a revival of the azobenzene class of hypoxia activated drugs, especially applied to theranostics, is warranted.
      13. URL :
        http://www.sciencedirect.com/science/article/pii/S0142961216306421
      14. Call Number :
        PKI @ catherine.lautenschlager @ 12904
      15. Serial :
        12826
      1. Author :
        Sahu, Abhishek; Lee, Jong Hyun; Lee, Hye Gyeong; Jeong, Yong Yeon; Tae, Giyoong
      2. Title :
        Prussian blue/serum albumin/indocyanine green as a multifunctional nanotheranostic agent for bimodal imaging guided laser mediated combinatorial phototherapy
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Journal of Controlled Release
      6. Products :
      7. Volume :
        236
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Theranostic;; Multifunctional nanoparticle;; Indocyanine green;; Prussian blue;; Photothermal therapy;; Photodynamic therapy; IVIS; IVIS FLI in vivo
      12. Abstract :
        Developing novel nanotheranostic agent using only clinically approved materials is highly desirable and challenging. In this study, we combined three clinically approved materials, Prussian blue (PB), serum albumin (BSA), and indocyanine green (ICG), by a simple and biocompatible method to prepare a multifunctional theranostic PB-BSA-ICG nanoparticle. The multifunctional nanoparticle system could provide dual mode magnetic resonance (MR) and near infrared (NIR) fluorescence imaging as well as combined photothermal and photodynamic (PTT-PDT) therapy in response to a single NIR laser. This nanoparticle showed an excellent stability in physiological solutions and could suppress the photo-instability of ICG. In the absence of light, the nanoparticles showed no cytotoxicity, but significant cell death was induced through combined PTT-PDT effect after irradiation with NIR laser light. A high tumor accumulation and minimal nonspecific uptake by other major organs of PB-BSA-ICG nanoparticle were observed in vivo, analyzed by T1-weighted MR and NIR fluorescence bimodal imaging in tumor xenograft mice after intravenous injection. The nanoparticles efficiently suppressed the tumor growth through combinatorial phototherapy with no tumor recurrence upon a single NIR laser irradiation. These results demonstrated that PB-BSA-ICG is potentially an interesting nanotheranostic agent for imaging guided cancer therapy by overcoming the limitations of each technology and enhancing the therapeutic efficiency as well as reducing side effects.
      13. URL :
        N/A
      14. Call Number :
        PKI @ user @ 11842
      15. Serial :
        19540
      1. Author :
        Li, Shi-Ying; Cheng, Hong; Xie, Bo-Ru; Qiu, Wen-Xiu; Song, Li-Lin; Zhuo, Ren-Xi; Zhang, Xian-Zheng
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        104
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Theranostic; Ratiometric imaging; Apoptosis imaging; FRET; Photodynamic therapy; IVIS; IVIS FLI in vivo
      12. Abstract :
        Feedback imaging-guided precise photodynamic therapy (PDT) can facilitate the development of personalized medicine. In this work, a Förster resonance energy transfer (FRET) based theranostic probe was fabricated for simultaneous tumor targeting PDT and ratiometric imaging of the therapeutic effect. The theranostic probe (designated as P-PpIX) was comprised of a targeting moiety, a caspase-3 responsive linker, a FRET fluorophore pair and a photosensitizer. It was found that P-PpIX exhibited low intrinsic background fluorescence due to the high FRET quenching efficiency. The Arg-Gly-Asp (RGD) targeting moiety allowed P-PpIX to selectively accumulate in αvβ3 integrin overexpressed tumor cells. Upon photo irradiation, the PDT effect of P-PpIX could induce cell death with apoptosis related mechanism, and the activated caspase-3 would subsequently cleave the Asp-Glu-Val-Asp (DEVD) peptide sequence to terminate the intramolecular FRET process. The activated caspase-3 expression and the real time therapeutic efficacy could be precisely assessed in situ by the fluorescence intensity ratio of the released 5(6)-carboxylfluorescein (FAM, reporter fluorescence) and protoporphyrin IX (PpIX, internal reference fluorescence). This novel ratiometric theranostic probe could provide the real-time feedback for precise PDT.
      13. URL :
        http://www.sciencedirect.com/science/article/pii/S0142961216303556
      14. Call Number :
        PKI @ user @ 12157
      15. Serial :
        19729
      1. Author :
        Kamalapuram, Sishir K; Kanwar, Rupinder K; Roy, Kislay; Chaudhary, Rajneesh; Sehgal, Rakesh; Kanwar, Jagat R
      2. Title :
        Theranostic multimodular potential of zinc-doped ferrite-saturated metal-binding protein-loaded novel nanocapsules in cancers
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        International Journal of Nanomedicine
      6. Products :
      7. Volume :
        11
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        theranostic,; multimodular cancer therapy,; nanocapsules,; nanomedicine,; real-time imaging; IVIS; IVIS FLI in vivo
      12. Abstract :
        The present study successfully developed orally deliverable multimodular zinc (Zn) iron oxide (Fe3O4)-saturated bovine lactoferrin (bLf)-loaded polymeric nanocapsules (NCs), and evaluated their theranostic potential (antitumor efficacy, magnetophotothermal efficacy and imaging capability) in an in vivo human xenograft CpG-island methylator phenotype (CIMP)-1+/CIMP2−/chromosome instability-positive colonic adenocarcinoma (Caco2) and claudin-low, triple-negative (ER-/PR-/HER2-; MDA-MB-231) breast cancer model. Mice fed orally on the Zn-Fe-bLf NC diet showed downregulation in tumor volume and complete regression in tumor volume after 45 days of feeding. In human xenograft colon cancer, vehicle-control NC diet-group (n=5) mice showed a tumor volume of 52.28±11.55 mm3, and Zn-Fe-bLf NC diet (n=5)-treated mice had a tumor-volume of 0.10±0.073 mm3. In the human xenograft breast cancer model, Zn-Fe-bLf NC diet (n=5)-treated mice showed a tumor volume of 0.051±0.062 mm3 within 40 days of feeding. Live mouse imaging conducted by near-infrared fluorescence imaging of Zn-Fe-bLf NCs showed tumor site-specific localization and regression of colon and breast tumor volume. Ex vivo fluorescence-imaging analysis of the vital organs of mice exhibited sparse localization patterns of Zn-Fe-bLf NCs and also confirmed tumor-specific selective localization patterns of Zn-Fe-bLf NCs. Dual imaging using magnetic resonance imaging and computerized tomography scans revealed an unprecedented theranostic ability of the Zn-Fe-bLf NCs. These observations warrant consideration of multimodular Zn-Fe-bLf NCs for real-time cancer imaging and simultaneous cancer-targeted therapy.
      13. URL :
        N/A
      14. Call Number :
        PKI @ user @ 11464
      15. Serial :
        19833
      1. Author :
        Kang, Yibin
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        TGF-β Signaling
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        TGFβ; Tumor stroma; Metastasis; Xenograft; Mammary fat pad injection; Intravenous injection; Intracardiac injection; Animal model; In vivo imaging; Bioluminescence; Luciferase; IVIS; IVIS BLI in vivo
      12. Abstract :
        Metastatic spread of cancer cells from the primary tumors to distant vital organs, such as lung, liver, brain, and bone, is responsible for the majority of cancer-related deaths. Development of metastatic lesions is critically dependent on the interaction of tumor cells with the stromal microenvironment. As a multifunctional paracrine signaling factor that is abundantly produced by both tumor and stromal cells, TGFβ has been well established as an important mediator of tumor–stromal interaction during cancer metastasis. Imaging the in vivo dynamic of TGFβ signaling activity during cancer metastasis is critical for understanding the pathogenesis of the disease, and for the development of effective anti-metastasis treatments. In this chapter, I describe several xenograft methods to introduce human breast cancer cells into nude mice in order to generate spontaneous and experimental metastases, as well as the luciferase-based bioluminescence imaging method for quantitative imaging analysis of TGFβ signaling in tumor cells during metastasis.
      13. URL :
        http://dx.doi.org/10.1007/978-1-4939-2966-5_13
      14. Call Number :
        PKI @ user @ 10332
      15. Serial :
        19826
      1. Author :
        Huber-Ruano, I.; Raventós, C.; Cuartas, I.; Sánchez-Jaro, C.; Arias, A.; Parra, J. L.; Wosikowski, K.; Janicot, M.; Seoane, J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Annals of Oncology
      6. Products :
      7. Volume :
        28
      8. Issue :
        9
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        TGF-β; lung metastasis; tumor-associated macrophages; CD86; antisense oligonucleotides; tumor microenvironment; IVIS
      12. Abstract :
        BackgroundThe transforming growth factor (TGF)-β pathway is a well-described inducer of immunosuppression and can act as an oncogenic factor in advanced tumors. Several preclinical and clinical studies show that the TGF-β pathway can be considered a promising molecular target for cancer therapy. The human genome has three TGF-β isoforms and not much is known about the oncogenic response to each of the isoforms. Here, we studied the antitumor response to ISTH0047, a recently developed locked nucleic acid-modified antisense oligonucleotide targeting TGF-β2.Materials and methodsWe have studied the anticancer response to ISTH0047 using gymnotic delivery in tumor cell cultures and in in vivo preclinical orthotopic mouse models for primary tumors (breast and kidney tumors) and lung metastasis.ResultsWe observed that ISTH0047 is able to significantly reduce TGF-β2 mRNA and protein levels without altering the levels of TGF-β1 and TGF-β3. ISTH0047 prevented lung metastasis in syngeneic orthotopic renal cell carcinoma (RENCA) and breast cancer (4T1) tumor models. In addition, using an orthotopic xenograft model of a lung cancer cell line (CRL5807) that mainly expresses TGF-β2, we observed that ISTH0047 had an important effect on the lung microenvironment inhibiting the growth of lung lesions. ISTH0047 treatment re-educated macrophages in the lung parenchyma to express the tumor-suppressive factor, CD86.ConclusionOverall, our data point to TGF-β2 as a therapeutic target and ISTH0047 as a novel anticancer drug to prevent lung metastasis by impacting on the tumor niche, in part, through the induction of CD86 in tumor-associated macrophages.
      13. URL :
        http://dx.doi.org/10.1093/annonc/mdx314 https://academic.oup.com/annonc/article-abstract/28/9/2278/4004846/An-antisense-oligonucleotide-targeting-TGF-2?redirectedFrom=fulltext
      14. Call Number :
        PKI @ catherine.lautenschlager @ 14123
      15. Serial :
        14027
      1. Author :
        Alam, Farzana; Al-Hilal, Taslim A; Park, Jooho; Choi, Jeong Uk; Mahmud, Foyez; Jeong, Jee-Heon; Kim, In-San; Kim, Sang Yoon; Hwang, Seung Rim; Byun, Youngro
      2. Title :
        Multi-stage inhibition in breast cancer metastasis by orally active triple conjugate, LHTD4 (low molecular weight heparin-taurocholate-tetrameric deoxycholate)
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        TGF-β1;; CXCL12;; polymeric bile acid;; low molecular weight heparin;; metastasis;; multi-stage targeting; IVIS; IVIS BLI in vivo
      12. Abstract :
        Targeting multiple stages in metastatic breast cancer is one of the effective ways to inhibit metastatic progression. To target human metastatic breast cancer as well as improving patient compliance, we developed an orally active low molecular weight heparin (LMWH)-taurocholate conjugated with tetrameric deoxycholic acid, namely LHTD4, which followed by physical complexation with a synthetic bile acid enhancer, DCK. In breast cancer, both transforming growth factor-β1 (TGF-β1) and CXCL12 exhibit enhanced metastatic activity during the initiation and progression stages of breast cancer, thus we direct the focus on investigating the antimetastatic effect of LHTD4/DCK complex by targeting TGF-β1 and CXCL12. Computer simulation study and SPR analysis were performed for the binding confirmation of LHTD4 with TGF-β1 and CXCL12. We carried out in vitro phosphorylation assays of the consecutive receptors of TGF-β1 and CXCL12 (TGF-β1R1 and CXCR4, respectively). Effects of LHTD4 on in vitro cell migration (induced by TGF-β1) and chemotaxis (mediated by CXCL12) were investigated. The in vivo anti-metastatic effect of LHTD4 was evaluated in an accelerated metastasis model and an orthotopic MDA-MB-231 breast cancer model. The obtained KD values of TGF-β1 and CXCL12 with LHTD4 were 0.85 and 0.019 μM respectively. The simulation study showed that binding affinities of LHTD4 fragment with either TGF-β1 or CXCL12 through additional electrostatic interaction was more stable than that of LMWH fragment. In vitro phosphorylation assays of TGF-β1R1 and CXCR4 showed that the effective inhibition of receptor phosphorylation was observed with the treatment of LHTD4. The expressions of epithelial to mesenchymal transition (EMT) marker proteins such as vimentin and Snail were prevented by LTHD4 treatment in in vitro studies with TGF-β1 treated MDA-MB-231 cells. Moreover, we observed that LHTD4 negatively regulated the functions of TGF-β1 and CXCL12 on migration and invasion of breast cancer cell. In several advanced orthotopic and experimental breast cancer metastasis murine models, the treatment with LHTD4 (5 mg/kg daily, p.o.) significantly inhibited metastasis compared to the control. Overall, LHTD4 exhibited anti-metastatic effects by inhibiting TGF-β1 and CXCL12, and the clinically relevant dose of orally active LHTD4 was found to be effective in preclinical studies without any apparent toxicity.
      13. URL :
        N/A
      14. Call Number :
        PKI @ user @ 10907
      15. Serial :
        20147
      1. Author :
        Luo, Jian; Wyss-Coray, Tony
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Bioluminescence
      6. Products :
      7. Volume :
        574
      8. Issue :
        N/A
      9. Page Numbers :
        193
      10. Research Area :
        N/A
      11. Keywords :
        TGF-?, Smad, bioluminescence imaging, in vivo, luciferase, immunofluorescence IVIS, Xenogen
      12. Abstract :
        TGF-beta signaling via the Smad2/3 pathway has key roles in development and tissue homeostasis. Perturbations of the TGF-beta signaling are involved in the pathogenesis of many human diseases, including cancer, fibrotic disorders, developmental defects, and neurodegeneration. To study the temporal and spatial patterns of Smad2/3-dependent signaling in living animals, we engineered transgenic mice with a Smad-responsive luciferase reporter (SBE-luc mice). Smad2/3-dependent signaling can be assessed non-invasively in living mice by bioluminescence imaging. To identify the cellular source of the bioluminescence signal, we generated new reporter mice expressing a trifusion protein containing luciferase, red fluorescent protein (RFP), and thymidine kinase under the control of the same SBE promoter (SBE-lucRT mice). SBE-luc and SBE-lucRT mice can be used to study temporal, tissue-specific activation of Smad2/3-dependent signaling in living mice as well as for the identification of endogenous or synthetic modulators of this pathway
      13. URL :
        http://www.springerprotocols.com/Abstract/doi/10.1007/978-1-60327-321-3_16
      14. Call Number :
        140764
      15. Serial :
        5511
      1. Author :
        Zschiebsch, Katja; Fischer, Caroline; Pickert, Geethanjali; Häeussler, Annett; Radeke, Heinfried; Grösch, Sabine; Ferreirós, Nerea; Geisslinger, Gerd; Werner, Ernst R; Tegeder, Irmgard
      2. Title :
        Tetrahydrobiopterin attenuates DSS-evoked colitis in mice by rebalancing redox and lipid signaling
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Journal of Crohn's and Colitis
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Tetrahydrobiopterin,; nitric oxide,; inflammatory bowel disease,; glycerophospholipids,; redox stress,; lipid signaling molecules,; AGMO; IVIS; IVIS BLI in vivo
      12. Abstract :
        Background and aims: GTP cyclohydrolase (GCH1) governs the production of the enzyme cofactor, tetrahydrobiopterin (BH4), which is essential for biogenic amine synthesis, lipid metabolism via alkylglycerol monooxygenase (AGMO) and redox coupling of nitric oxide synthases (NOSs). Inflammation-evoked unequal regulations of GCH1 and NOS or AGMO may cause redox stress and lipid imbalances. Methods: The present study assessed potential therapeutic effects of rebalancing these systems with BH4 in experimental colitis in mice. Results: Oral treatment with BH4 as suspension of crushed tablets attenuated colitis whereas inhibition of its production had opposite effects i.e. aggravated weight loss, epithelial hemorrhages and ulcers, neutrophil infiltrates, production of reactive oxygen species and unfavorable profile changes of endocannabinoids, ceramides and lysophosphatidic acids. Oppositely, oral BH4 normalized biopterin, reduced in vivo activity of oxidases and peroxidases in the inflamed gut, favoured nitric oxide over hydrogen peroxide and maintained normal levels of lipid signalling molecules. BH4 favoured thereby resident CD3+CD8+ and regulatory CD3+CD25+ intraepithelial T-cells that are important for epithelial integrity. Conclusions: BH4 protected against colitis in mice via two major pathways: (i) by reduction of oxidative stress and (ii) by re-orchestration of alkyl- and acylglycerolipid signaling via AGMO. Oral treatment with BH4 is a safe approved supplementary therapy for genetic BH4 deficiency and did not excessively increase systemic BH4 levels. Therefore, one may consider repurposing of oral BH4 as an adjunctive treatment for colitis.
      13. URL :
        N/A
      14. Call Number :
        PKI @ user @ 11187
      15. Serial :
        19255
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