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      1. Author :
        Xie, Chao; Liang, Bojian; Xue, Ming; Lin, Angela S.P.; Loiselle, Alayna; Schwarz, Edward M.; Guldberg, Robert E.; O'Keefe, Regis J.; Zhang, Xinping
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Am J Pathol
      6. Products :
      7. Volume :
        175
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen10, Xen 10, Streptococcus pneumoniae Xen10, IVIS
      12. Abstract :
        Although the essential role of cyclooxygenase (COX)-2 in fracture healing is known, the targeted genes and molecular pathways remain unclear. Using prostaglandin E2 receptor (EP)2 and EP4 agonists, we examined the effects of EP receptor activation in compensation for the lack of COX-2 during fracture healing. In a fracture-healing model, COX-2-/- mice showed delayed initiation and impaired endochondral bone repair, accompanied by a severe angiogenesis deficiency. The EP4 agonist markedly improved the impaired healing in COX-2-/- mice, as evidenced by restoration of bony callus formation on day 14, a near complete reversal of bone formation, and an approximately 70% improvement of angiogenesis in the COX-2-/- callus. In comparison, the EP2 agonist only marginally enhanced bone formation in COX-2-/- mice. To determine the differential roles of EP2 and EP4 receptors on COX-2-mediated fracture repair, the effects of selective EP agonists on chondrogenesis were examined in E11.5 long-term limb bud micromass cultures. Only the EP4 agonist significantly increased cartilage nodule formation similar to that observed during prostaglandin E2 treatment. The prostaglandin E2/EP4 agonist also stimulated MMP-9 expression in bone marrow stromal cell cultures. The EP4 agonist further restored the reduction of MMP-9 expression in the COX-2-/- fracture callus. Taken together, our studies demonstrate that EP2 and EP4 have differential functions during endochondral bone repair. Activation of EP4, but not EP2 rescued impaired bone fracture healing in COX-2-/- mice.
      13. URL :
        http://ajp.amjpathol.org/cgi/content/abstract/175/2/772
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10401
      1. Author :
        Shi, Yang; Kunjachan, Sijumon; Wu, Zhuojun; Gremse, Felix; Moeckel, Diana; van Zandvoort, Marc; Kiessling, Fabian; Storm, Gert; van Nostrum, Cornelus F.; Hennink, Wim E.; Lammers, Twan
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2015
      5. Publication :
        Nanomedicine
      6. Products :
      7. Volume :
        10
      8. Issue :
        7
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Fmt
      12. Abstract :
        Aim: To enable multimodal in vivo and ex vivo optical imaging of the biodistribution and tumor accumulation of core-crosslinked polymeric micelles (CCPMs). Materials & methods: mPEG-b-p(HPMAm-Lac)-based polymeric micelles, core-crosslinked via cystamine and covalently labeled with two different fluorophores (Dy-676/488), were synthesized. The CCPMs were intravenously injected into CT26 tumor-bearing mice. Results: Upon intravenous injection, the CCPMs accumulated in CT26 tumors reasonably efficiently, with values reaching approximately 4%ID at 24 h. Ex vivo two-photon laser scanning microscopy confirmed efficient extravasation of the image-guided CCPMs out of tumor blood vessels and relatively deep penetration into the tumor interstitium. Conclusion: CCPMs were labeled with multiple fluorophores, and the results obtained exemplify that combining several different in vivo and ex vivo optical imaging techniques is highly useful for analyzing the biodistribution and tumor accumulation of nanomedicines.
      13. URL :
        http://dx.doi.org/10.2217/nnm.14.170
      14. Call Number :
        PKI @ catherine.lautenschlager @ 9429
      15. Serial :
        13474
      1. Author :
        Klyachko, Natalia L; Haney, Matthew J; Zhao, Yuling; Manickam, Devika S; Mahajan, Vivek; Suresh, Poornima; Hingtgen, Shawn D; Mosley, R Lee; Gendelman, Howard E; Kabanov, Alexander V
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2013
      5. Publication :
        Nanomedicine
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS Imaging
      12. Abstract :
        Abstract
        AIMS:
        Active targeted transport of the nanoformulated redox enzyme, catalase, in macrophages attenuates oxidative stress and as such increases survival of dopaminergic neurons in animal models of Parkinson's disease. Optimization of the drug formulation is crucial for the successful delivery in living cells. We demonstrated earlier that packaging of catalase into a polyion complex micelle ('nanozyme') with a synthetic polyelectrolyte block copolymer protected the enzyme against degradation in macrophages and improved therapeutic outcomes. We now report the manufacture of nanozymes with superior structure and therapeutic indices.

        METHODS:
        Synthesis, characterization and therapeutic efficacy of optimal cell-based nanoformulations are evaluated.

        RESULTS:
        A formulation design for drug carriers typically works to avoid entrapment in monocytes and macrophages focusing on small-sized nanoparticles with a polyethylene glycol corona (to provide a stealth effect). By contrast, the best nanozymes for delivery in macrophages reported in this study have a relatively large size (≈ 200 nm), which resulted in improved loading capacity and release from macrophages. Furthermore, the cross-linking of nanozymes with the excess of a nonbiodegradable linker ensured their low cytotoxicity, and efficient catalase protection in cell carriers. Finally, the 'alternatively activated' macrophage phenotype (M2) utilized in these studies did not promote further inflammation in the brain, resulting in a subtle but statistically significant effect on neuronal regeneration and repair in vivo.

        CONCLUSION:
        The optimized cross-linked nanozyme loaded into macrophages reduced neuroinflammatory responses and increased neuronal survival in mice. Importantly, the approach for nanoformulation design for cell-mediated delivery is different from the common requirements for injectable formulations.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 6719
      15. Serial :
        14383
      1. Author :
        Lemarie, F.; Chang, C. W.; Blatchford, D. R.; Amor, R.; Norris, G.; Tetley, L.; McConnell, G.; Dufes, C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nanomedicine (Lond)
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc
      12. Abstract :
        Aim: The therapeutic potential of epigallocatechin-3-gallate (EGCG), a green tea polyphenol with anticancer properties, is limited by its inability to specifically reach tumors following intravenous administration. The purpose of this study was to determine whether a tumor-targeted vesicular formulation of EGCG would suppress the growth of A431 epidermoid carcinoma and B16-F10 melanoma in vitro and in vivo. Materials & methods: Transferrin-bearing vesicles encapsulating EGCG were administered intravenously to mice bearing subcutaneous A431 and B16-F10 tumors. Results: The intravenous administration of EGCG encapsulated in transferrin-bearing vesicles resulted in tumor suppression in 40% of A431 and B16-F10 tumors. Animal survival was improved by more than 20 days compared with controls. Conclusion: Encapsulation of EGCG in transferrin-bearing vesicles is a promising therapeutic strategy. Original submitted 28 November 2011; Revised submitted 11 May 2012.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22891867
      14. Call Number :
        PKI @ kd.modi @ 14
      15. Serial :
        10532
      1. Author :
        Lu, Z.; Dai, T.; Huang, L.; Kurup, D. B.; Tegos, G. P.; Jahnke, A.; Wharton, T.; Hamblin, M. R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Nanomedicine (Lond)
      6. Products :
      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen5, Xen 5, Pseudomonas aeruginosa Xen 5, Animals; Fullerenes/*chemistry; Male; Mice; Mice, Inbred BALB C; Photochemotherapy/*methods; Photosensitizing Agents/*chemistry; Pseudomonas Infections/*drug therapy; Pseudomonas aeruginosa/drug effects; Wound Infection/*drug therapy
      12. Abstract :
        AIMS: Fullerenes are under intensive study for potential biomedical applications. We have previously reported that a C60 fullerene functionalized with three dimethylpyrrolidinium groups (BF6) is a highly active broad-spectrum antimicrobial photosensitizer in vitro when combined with white-light illumination. We asked whether this high degree of in vitro activity would translate into an in vivo therapeutic effect in two potentially lethal mouse models of infected wounds. MATERIALS & METHODS: We used stable bioluminescent bacteria and a low light imaging system to follow the progress of the infection noninvasively in real time. An excisional wound on the mouse back was contaminated with one of two bioluminescent Gram-negative species, Proteus mirabilis (2.5 x 10(7) cells) and Pseudomonas aeruginosa (5 x 10(6) cells). A solution of BF6 was placed into the wound followed by delivery of up to 180 J/cm(2) of broadband white light (400-700 nm). RESULTS: In both cases there was a light-dose-dependent reduction of bioluminescence from the wound not observed in control groups (light alone or BF6 alone). Fullerene-mediated photodynamic therapy of mice infected with P. mirabilis led to 82% survival compared with 8% survival without treatment (p < 0.001). Photodynamic therapy of mice infected with highly virulent P. aeruginosa did not lead to survival, but when photodynamic therapy was combined with a suboptimal dose of the antibiotic tobramycin (6 mg/kg for 1 day) there was a synergistic therapeutic effect with a survival of 60% compared with a survival of 20% with tobramycin alone (p < 0.01). CONCLUSION: These data suggest that cationic fullerenes have clinical potential as an antimicrobial photosensitizer for superficial infections where red light is not needed to penetrate tissue.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21143031
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10390
      1. Author :
        Zhang, Mingzhen; Wang, Xiaoyu; Han, Moon Kwon; Merlin, James F Collins & Didier
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Nanomedicine
      6. Products :
      7. Volume :
        12
      8. Issue :
        16
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        ginger-derived lipids vehicles; natural delivery system; oral administration; siRNA; IVIS; IVIS FLI
      12. Abstract :
        Aim: To develop novel siRNA delivery system overcoming the limitations of synthetic nanoparticles, such as potential side effects, nonspecificity and economic production for ulcerative colitis therapy. Materials & methods: Nanoparticles composed of edible ginger-derived lipid, termed ginger-derived lipid vehicles (GDLVs) were generated from ginger lipids through hydration of a lipid film, a commonly used method for a liposome fabrication. The morphology, biocompatibility and transfection efficiency of GDLVs loaded with siRNA-CD98 (siRNA-CD98/GDLVs) were characterized by standard methods. Results: Orally administered siRNA-CD98/GDLVs were effectively targeted specifically to colon tissues, resulting in reduced expression of CD98. Conclusion: These GDLVs have great promise as efficient siRNA-delivery vehicles while potentially obviating issues related to the traditional synthetic nanoparticles. As such, they help shift the current paradigm of siRNA delivery away from artificially synthesized nanoparticles toward the use of naturally derived nanovehicles from edible plants.
      13. URL :
        https://www.futuremedicine.com/doi/abs/10.2217/nnm-2017-0196
      14. Call Number :
        PKI @ catherine.lautenschlager @ 14045
      15. Serial :
        13569
      1. Author :
        dos Santos Câmara, Ana Lygia; ‡, Gregor Nagel; Tschiche, Harald R; Cardador, Camila Magalhães; Muehlmann, Luis Alexandre; Oliveira, Daniela Mara de; Alvim, Paula Queiroz; Azevedo, Ricardo Bentes; Calderón, Marcelo; Longo, João Paulo Figueiró
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Nanomedicine
      6. Products :
      7. Volume :
        12
      8. Issue :
        15
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        breast cancer; doxorubicin; drug delivery; metastasis; nanoemulsion; pH-sensitive; IVIS; IVIS BLI in vitro; IVIS BLI in vivo
      12. Abstract :
        Aim: To develop an acid-sensitive lipidated, doxorubicin (Dox) prodrug (C16-Dox) to be entrapped in lipid nanoemulsion (NE-C16-Dox) as a nanocarrier to treat breast cancer models (in vitro and in vivo). Results: We report the efficacy of NE-C16-Dox in in vitro experiments, as well as the improved chemotherapeutic index and tumor-control efficacy compared with treatment with free Dox in an in vivo murine 4T1 breast cancer model. In addition, NE-C16-Dox allowed the use of a higher dose of Dox, acceptable biocompatibility and a significant reduction in lung metastasis. Conclusion: Taken together, these results indicate that NE-C16-Dox is promising for breast cancer treatment, thus creating possibilities to translate these nanotechnology concepts to clinical applications.
      13. URL :
        https://www.futuremedicine.com/doi/abs/10.2217/nnm-2017-0091
      14. Call Number :
        PKI @ catherine.lautenschlager @ 14096
      15. Serial :
        14118
      1. Author :
        Babaei, Maryam; Abnous, Khalil; Taghdisi, Seyed Mohammad; Farzad, Sara Amel; Peivandi, Mohammad Taghi; Ramezani, Mohammad; Alibolandi, Mona
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Nanomedicine
      6. Products :
      7. Volume :
        12
      8. Issue :
        11
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        5-fluorouracil; aptamer; EpCAM; gatekeeper; gold nanoparticles; silica; IVIS; IVIS FLI in vivo
      12. Abstract :
        Aim: In this study, we report the fabrication of epithelial cell adhesion molecule targeted 5-fluorouracil (5-FU) encapsulated PEGylated mesoporous silica nanoparticles (NPs) hybridized with gold NPs (PEG-Au@Si-5-FU) as gatekeeper for theranostic applications. Materials & methods: The prepared targeted and nontargeted formulations were evaluated in vitro in terms of their cellular internalization and toxicity. The prepared theranostic hybrid system was also implemented for computed tomography of HepG2 tumor-bearing nude mice in vivo. Results: Fluorescence microscopy and MTT assay demonstrated that the developed epithelial cell adhesion molecule-PEG-Au@Si-5-FU had higher cytotoxicity than nontargeted PEG-Au@Si-5-FU in 2D and 3D HepG2 cell cultures. Moreover, the targeted hybrid system was preferentially accumulated in HepG2 tumor cells in vitro and in vivo. Conclusion: This work introduces a novel strategy for developing multimodal NPs via nanoparticulate hybrid materials.
      13. URL :
        https://www.futuremedicine.com/doi/abs/10.2217/nnm-2017-0028
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13898
      15. Serial :
        14210
      1. Author :
        Wang, Kaikai; ‡, Gang Chen; Hu, Qi; Zhen, Yuqian; Li, Huipeng; Chen, Jiao; Di, Bin; Hu, Yiqiao; Sun, Minjie; Oupický, David
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Nanomedicine
      6. Products :
      7. Volume :
        12
      8. Issue :
        9
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        hemoglobin; IR780; oral-photothermal therapy; protein nanoparticles; IVIS; IVIS FLI in vivo
      12. Abstract :
        Aim: The aim of the present study was to use hemoglobin (Hb) nanoparticles (NPs) to improve oral bioavailability of a near-infrared dye IR780 for in vivo antitumor application in photothermal therapy. Methods: One-step acid-denaturing method was used to encapsulate IR780 into self-assembled Hb NPs (IR780@Hb NPs). Pharmacokinetics, biodistribution and antitumor effect were studied in vivo. Results: The Hb NPs showed high stability in enzymatic and acidic conditions similar to the gastric environment, and enhanced absorption of IR780 into the blood. In vivo imaging revealed that IR780 could accumulate at the tumor sites and effectively caused photothermal effect, which resulted in tumor ablation after oral administration in tumor-bearing mice. Conclusion: Hb NPs represent a promising delivery system for improving oral absorption of photosensitizer dyes, which could open new treatment modalities in cancer.
      13. URL :
        https://www.futuremedicine.com/doi/abs/10.2217/nnm-2016-0411
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13763
      15. Serial :
        13657
      1. Author :
        Zhang, Jing; Wang, Tianqi; Mu, Shengjun; Olerile, Livesey D; Yu, Xiaoyue; Zhang, Na
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Nanomedicine
      6. Products :
      7. Volume :
        12
      8. Issue :
        8
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        biomacromolecule/lipid hybrid nanoparticles; enzyme-responsive; HCC; hyaluronic acid; sorafenib; IVIS; IVIS FLI in vivo
      12. Abstract :
        Aim: Hybrids composed of various materials are highly versatile for drug delivery in tumor therapy including hepatocellular carcinoma. Herein, a sorafenib (SF)-loaded biomacromolecule hyaluronic acid (HA)/lipid hybrid nanoparticles (HA/SF-cLNS) were developed for targeting drug delivery. Materials & methods: In vitro assays determined HA/SF-cLNS release behavior, enzymatic degradation, uptake and cytotoxicity. H22-bearing liver cancer xenograft murine models were used to evaluate the biodistribution and therapeutic efficacy in vivo. Results: HA/SF-cLNS could be disassembled and drug was released in response to hyaluronidase. In vivo imaging results demonstrated HA/cLNS could enhance drug accumulation at tumor site. Meanwhile, HA/SF-cLNS exhibited improved antitumor efficacy in vitro and in vivo. Conclusion: HA/SF-cLNS demonstrated the potential to enhance antitumor efficacy of SF.
      13. URL :
        https://www.futuremedicine.com/doi/abs/10.2217/nnm-2016-0402
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13559
      15. Serial :
        13574
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