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      1. Author :
        Shen, Yurun; Hu, Mengying; Qiu, Liyan
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Nanomedicine
      6. Products :
      7. Volume :
        11
      8. Issue :
        23
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Maestro
      12. Abstract :
        Aim: In this study, we constructed a novel vector (BioPf-M-loaded Alg-microparticles [Alg-BioPf-M]) with nano-in-micro structure to improve the oral absorption of docetaxel (DTX) by sequentially dual-targeting functions toward intestine and sodium-dependent multivitamin transporter based on entrapping biotin-modified micelles into alginate microparticles. Methods: A series of characteristics of this system was investigated, such as drug release, cellular uptake, transport pathway and the comprehensive in vivo studies including pharmacokinetic studies, anti-tumor activity and toxicity study. Results: The bioavailability of DTX-loaded Alg-BioPf-M was 27.4-fold higher than that of free DTX after oral administration and achieved superior tumor inhibition of 84.6% against sarcoma 180 tumors. Conclusion: These results demonstrated that the Alg-BioPf-M was a promising vector for oral delivery of DTX.
      13. URL :
        http://dx.doi.org/10.2217/nnm-2016-0259
      14. Call Number :
        PKI @ catherine.lautenschlager @ 12686
      15. Serial :
        12919
      1. Author :
        Cano-Garrido, Olivia; Céspedes, María Virtudes; Unzueta, Ugutz; Saccardo, Paolo; Roldán, Mònica; Sánchez-Chardi, Alejandro; Cubarsi, Rafael; Vázquez, Esther; Mangues, Ramon; García-Fruitós, Elena; Villaverde, Antonio
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Nanomedicine
      6. Products :
      7. Volume :
        11
      8. Issue :
        18
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        proteinnanoparticles; recombinantproteins; tumor-homingpeptides; IVIS; IVIS FLI ex vivo
      12. Abstract :
        Lactococcus lactis is a Gram-positive (endotoxin-free) food-grade bacteria exploited as alternative to Escherichia coli for recombinant protein production. We have explored here for the first time the ability of this platform as producer of complex, self-assembling protein materials. Materials & methods: Biophysical properties, cell penetrability and in vivo biodistribution upon systemic administration of tumortargeted protein nanoparticles produced in L. lactis have been compared with the equivalent material produced in E. coli. Results: Protein nanoparticles have been efficiently produced in L. lactis, showing the desired size, internalization properties and biodistribution. Conclusion: In vitro and in vivo data confirm the potential and robustness of the production platform, pointing out L. lactis as a fascinating cell factory for the biofabrication of protein materials intended for therapeutic applications.
      13. URL :
        http://dx.doi.org/10.2217/nnm-2016-0200
      14. Call Number :
        PKI @ user @ 12312
      15. Serial :
        20091
      1. Author :
        Afzal, Syed Muzammil; Shareef, Mohammad Zubair; Dinesh, Tummuri; Kishan, Veerabrahma
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Nanomedicine
      6. Products :
      7. Volume :
        11
      8. Issue :
        16
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS; IVIS FLI in vivo
      12. Abstract :
        To develop a folate-based docetaxel lipid nanoemulsion (FLNE) for tumor-targeted treatment. Materials & methods: The docetaxel LNEs were prepared and characterized. In vitro cytotoxic and cell uptake studies were performed. The tissue distribution and targeting of drug were studied by fluorescence imaging and tumor regression in mice. Results: The IC50 values of FLNE on cancer cells were significant. The cell uptake studies showed an increase in fluorescence with time. Imaging studies found that FLNE was superior in tumor targeting by 4.81- and 2.08-fold over controls. The tumor regression proved the superiority of FLNEs. Conclusion: The folate strategy was superior over PEGylation, albumin and transferrin strategies. The study demonstrated great potential of FLNE as a prospective targeted delivery system.
      13. URL :
        http://dx.doi.org/10.2217/nnm-2016-0120
      14. Call Number :
        PKI @ user @ 12196
      15. Serial :
        20157
      1. Author :
        Sarcinelli, Michelle Alvares; Albernaz, Marta de Souza; Szwed, Marzena; Iscaife, Alexandre; Leite, Kátia Ramos Moreira; Junqueira, Mara de Souza; Bernardes, Emerson Soares; da Silva, Emerson Oliveira; Tavares, Maria Ines Bruno; Santos-Oliveira, Ralph
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        OncoTargets and therapy
      6. Products :
      7. Volume :
        9
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS; IVIS BLI in vivo
      12. Abstract :
        Monoclonal antibodies as polymeric nanoparticles are quite interesting and endow this new drug category with many advantages, especially by reducing the number of adverse reactions and, in the case of radiopharmaceuticals, also reducing the amount of radiation (dose) administered to the patient. In this study, a nanoradiopharmaceutical was developed using polylactic acid (PLA)/polyvinyl alcohol (PVA)/montmorillonite (MMT)/trastuzumab nanoparticles labeled with technetium-99m (99mTc) for breast cancer imaging. In order to confirm the nanoparticle formation, atomic force microscopy and dynamic light scattering were performed. Cytotoxicity of the nanoparticle and biodistribution with 99mTc in healthy and inducted animals were also measured. The results from atomic force microscopy showed that the nanoparticles were spherical, with a size range of ~200–500 nm. The dynamic light scattering analysis demonstrated that over 90% of the nanoparticles produced had a size of 287 nm with a zeta potential of −14,6 mV. The cytotoxicity results demonstrated that the nanoparticles were capable of reaching breast cancer cells. The biodistribution data demonstrated that the PLA/PVA/MMT/trastuzumab nanoparticles labeled with 99mTc have great renal clearance and also a high uptake by the lesion, as ~45% of the PLA/PVA/MMT/trastuzumab nanoparticles injected were taken up by the lesion. The data support PLA/PVA/MMT/trastuzumab labeled with 99mTc nanoparticles as nanoradiopharmaceuticals for breast cancer imaging.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045224/ https://www.dovepress.com/getfile.php?fileID=32613
      14. Call Number :
        PKI @ user @ 12616
      15. Serial :
        19533
      1. Author :
        Jia, Tingting; Sun, Zhiguo; Lu, Ying; Gao, Jie; Zou, Hao; Xie, Fangyuan; Zhang, Guoqing; Xu, Hao; Sun, Duxin; Yu, Yuan; Zhong, Yanqiang
      2. Title :
      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 :
        IVIS; IVIS FLI in vivo; IVIS FLI ex vivo
      12. Abstract :
        Due to the impermeability of the blood–brain barrier and the nonselective distribution of drugs in the brain, the therapeutic access to intractable neurological disorders is challenging. In this study, dual brain-targeting polymersomes (POs) functionalized by transferrin and Tet-1 peptide (Tf/Tet-1-POs) promoted the transportation of curcumin into the brain and provided neuroprotection. The modification of the ligands that bind to the surface of POs was revealed by X-ray photoelectron spectroscopy analysis. The cell uptake of a coculture model of mouse brain capillary endothelial cells with neurons showed that the Tf/Tet-1-POs had significant transportation properties and possessed affinity for neurons. The pharmacokinetic analysis showed that the blood–brain barrier permeability–surface efficiency of the Tf/Tet-1-POs was 0.28 mL/h/g and that the brain tissue uptake rate (% ID/g) was 0.08, which were significant compared with the controls (P<0.05). The curcumin-encapsulated Tf/Tet-1-POs provided neuroprotection and ameliorated cognitive dysfunction in intrahippocampal amyloid-β(1–42)-injected mice. These results suggest that the dual brain-targeting POs are more capable of drug delivery to the brain that can be exploited as a multiple noninvasive vehicle for targeting therapeutics.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981163/
      14. Call Number :
        PKI @ user @ 12321
      15. Serial :
        19847
      1. Author :
        Al Faraj, Achraf; Shaik, Abjal Pasha; Shaik, Asma Sultana
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2015
      5. Publication :
        International Journal of Nanomedicine
      6. Products :
      7. Volume :
        10
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        carbon nanotubes,; drug delivery systems,; magnetic resonance imaging,; diffusion-weighted MRI,; breast cancer,; nanomedicine; IVIS; IVIS BLi in vivo
      12. Abstract :
        PURPOSE: Targeting doxorubicin (DOX) by means of single-walled carbon nanotube (SWCNT) nanocarriers may help improve the clinical utility of this highly active therapeutic agent. Active targeting of SWCNTs using tumor-specific antibody and magnetic attraction by tagging the nanotubes with iron oxide nanoparticles can potentially reduce the unnecessary side effects and provide enhanced theranostics. In the current study, the in vitro and in vivo efficacy of DOX-loaded SWCNTs as theranostic nanoprobes was evaluated in a murine breast cancer model. METHODS: Iron-tagged SWCNTs conjugated with Endoglin/CD105 antibody with or without DOX were synthetized and extensively characterized. Their biocompatibility was assessed in vitro in luciferase (Luc2)-expressing 4T1 (4T1-Luc2) murine breast cancer cells using TiterTACS™ Colorimetric Apoptosis Detection Kit (apoptosis induction), poly (ADP-ribose) polymerase (marker for DNA damage), and thiobarbituric acid-reactive substances (oxidative stress generation) assays, and the efficacy of DOX-loaded SWCNTs was evaluated by measuring the radiance efficiency using bioluminescence imaging (BLI). Tumor progression and growth were monitored after 4T1-Luc2 cells inoculation using noninvasive BLI and magnetic resonance imaging (MRI) before and after subsequent injection of SWCNT complexes actively and magnetically targeted to tumor sites. RESULTS: Significant increases in apoptosis, DNA damage, and oxidative stress were induced by DOX-loaded SWCNTs. In addition, a tremendous decrease in bioluminescence was observed in a dose- and time-dependent manner. Noninvasive BLI and MRI revealed successful tumor growth and subsequent attenuation along with metastasis inhibition following DOX-loaded SWCNTs injection. Magnetic tagging of SWCNTs was found to produce significant discrepancies in apparent diffusion coefficient values providing a higher contrast to detect treatment-induced variations as noninvasive imaging biomarker. In addition, it allowed their sensitive noninvasive diagnosis using susceptibility-weighted MRI and their magnetic targeting using an externally applied magnet. CONCLUSION: Enhanced therapeutic efficacy of DOX delivered through antibody-conjugated magnetic SWCNTs was achieved. Further, the superiority of apparent diffusion coefficient measurements using diffusion-weighted MRI was found to be a sensitive imaging biomarker for assessment of treatment-induced changes.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278781/
      14. Call Number :
        PKI @ user @ 8852
      15. Serial :
        21053
      1. Author :
        Liu, Xu-Jie; Li, Liang; Liu, Xiu-Jun; Li, Yi; Zhao, Chun-Yan; Wang, Rui-Qi; Zhen, Yong-Su
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        International Journal of Nanomedicine
      6. Products :
      7. Volume :
        12
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS; IVIS FLI in vivo
      12. Abstract :
        Previous studies have shown that mithramycin A (MIT) is a promising candidate for the treatment of pancreatic carcinoma through inhibiting transcription factor Sp1. However, systemic toxicities may limit its clinical application. Here, we report a rationally designed formulation of MIT-loaded nanoparticles (MIT-NPs) with a small size and sustained release for improved passive targeting and enhanced therapeutic efficacy. Nearly spherical MIT-NPs with a mean particle size of 25.0±4.6 nm were prepared by encapsulating MIT into methoxy poly(ethylene glycol)-block-poly(d,l-lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles (NPs) with drug loading of 2.11%±0.51%. The in vitro release of the MIT-NPs lasted for >48 h with a sustained-release pattern. The cytotoxicity of MIT-NPs to human pancreatic cancer BxPC-3 and MIA Paca-2 cells was comparable to that of free MIT. Determined by flow cytometry and confocal microscopy, the NPs internalized into the cells quickly and efficiently, reaching the peak level at 1–2 h. In vivo fluorescence imaging showed that the prepared NPs were gradually accumulated in BxPC-3 and MIA Paca-2 xenografts and retained for 168 h. The fluorescence intensity in both BxPC-3 and MIA Paca-2 tumors was much stronger than that of various tested organs. Therapeutic efficacy was evaluated with the poorly permeable BxPC-3 pancreatic carcinoma xenograft model. At a well-tolerated dose of 2 mg/kg, MIT-NPs suppressed BxPC-3 tumor growth by 96%. Compared at an equivalent dose, MIT-NPs exerted significantly higher therapeutic effect than free MIT (86% versus 51%, P<0.01). Moreover, the treatment of MIT and MIT-NPs reduced the expression level of oncogene c-Myc regulated by Sp1, and notably, both of them decreased the protein level of CD47. In summary, the novel formulation of MIT-NPs shows highly therapeutic efficacy against pancreatic carcinoma xenograft. In addition, MIT-NPs can downregulate CD47 expression, implying that it might play a positive role in cancer immunotherapy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533565/ https://www.dovepress.com/getfile.php?fileID=37586
      14. Call Number :
        PKI @ catherine.lautenschlager @ 14170
      15. Serial :
        13918
      1. Author :
        Gao, Fei; Zhang, Jinming; Fu, Chaomei; Xie, Xiaoming; Peng, Fu; You, Jieshu; Tang, Hailin; Wang, Zhiyu; Li, Peng; Chen, Jianping
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        International Journal of Nanomedicine
      6. Products :
      7. Volume :
        12
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS; IVIS FLI in vivo
      12. Abstract :
        Isoliquiritigenin (ISL), a natural anti-breast cancer dietary compound, has poor delivery characteristics and low bioavailability. In order to promote the therapeutic outcome of ISL, a tumor-targeting lipid–polymer hybrid nanoparticle (NP) system modified by tumor-homing iRGD peptides has been developed. The hybrid NPs were prepared by a modified single-step nanoprecipitation method to encapsulate ISL. iRGD peptides were anchored on the surface by a postinsertion method (ISL-iRGD NPs). The stable lipid–polymer structure of ISL-iRGD NPs, with high encapsulation and loading efficiency, was confirmed. Compared to free ISL and non-iRGD-modified counterparts, ISL-iRGD NPs showed higher cytotoxicity and cell apoptosis against the different type of breast cancer cells. This was attributable to higher cellular accumulation mediated by the iRGD-integrin recognition and the nanoscale effect. More importantly, based on the active tumor-tissue accumulation by iRGD peptides and the prolonged in vivo circulation by the stealth nanostructure, ISL-iRGD NPs displayed higher tumor-growth inhibition efficiency in 4T1-bearing breast-tumor mouse models. Therefore, the constructed iRGD modified lipid–polymer hybrid NPs would provide a promising drug-delivery strategy to improve ISL in anti-breast cancer efficacy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459978/ https://www.dovepress.com/getfile.php?fileID=36780
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13994
      15. Serial :
        14086
      1. Author :
        Su, Yonghua; Huang, Nian; Chen, Di; Zhang, Li; Dong, Xia; Sun, Yun; Zhu, Xiandi; Zhang, Fulei; Gao, Jie; Wang, Ying; Fan, Kexing; Lo, Puichi; Li, Wei; Ling, Changquan
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        International Journal of Nanomedicine
      6. Products :
      7. Volume :
        12
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS; IVIS FLI IN vivo
      12. Abstract :
        The Chinese traditional medicine Shikonin is an ideal drug due to its multiple targets to tumor cells. But in clinics, improving its aqueous solubility and tumor accumulation is still a challenge. Herein, a copolymer with tunable poly(N-isopropylacrymaide) and polylactic acid block lengths is designed, synthesized, and characterized in nuclear magnetic resonance. The corresponding thermosensitive nanomicelle (TN) with well-defined core-shell structure is then assembled in an aqueous solution. For promoting the therapeutic index, the physical-chemistry properties of TNs including narrow size, low critical micellar concentration, high serum stability, tunable volume phase transition temperature (VPTT), high drug-loading capacity, and temperature-controlled drug release are systematically investigated and regulated through the fine self-assembly. The shikonin is then entrapped in a degradable inner core resulting in a shikonin-loaded thermosensitive nanomicelle (STN) with a VPTT of ~40°C. Compared with small-molecular shikonin, the in vitro cellular internalization and cytotoxicity of STN against breast cancer cells (Michigan Cancer Foundation-7) are obviously enhanced. In addition, the therapeutic effect is further enhanced by the programmed cell death (PCD) specifically evoked by shikonin. Interestingly, both the proliferation inhibition and PCD are synergistically promoted as T > VPTT, namely the temperature-regulated passive targeting. Consequently, as intravenous injection is administered to the BALB/c nude mice bearing breast cancer, the intratumor accumulation of STNs is significantly increased as T > VPTT, which is regulated by the in-house developed heating device. The in vivo antitumor assays against breast cancer further confirm the synergistically enhanced therapeutic efficiency. The findings of this study indicate that STN is a potential effective nanoformulation in clinical cancer therapy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457155/ https://www.dovepress.com/getfile.php?fileID=36732
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13975
      15. Serial :
        13728
      1. Author :
        Li, Ming-Ming; Cao, Jia; Yang, Jia-Chun; Shen, Yu-Jie; Cai, Xiao-Lei; Chen, Yuan-Wen; Qu, Chun-Ying; Zhang, Yi; Shen, Feng; Xu, Lei-Ming
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        International Journal of Nanomedicine
      6. Products :
      7. Volume :
        12
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS; IVIS FLI in vivo
      12. Abstract :
        Quantum dots (QDs) conjugated with integrin antagonist arginine–glycine–aspartic acid (RGD) peptides (QDs-RGD) are novel nanomaterials with a unique optical property: a high molar extinction coefficient. Previously, we have shown that QDs-RGD demonstrate a photodynamic therapy (PDT) effect as new photosensitizers for the pancreatic cancer cell line SW1990 in vitro. Here, we investigate the application of QDs-RGD in mice bearing pancreatic tumors using PDT. To ensure that more photosensitizers accumulated in tumors, QDs-RGD were injected intratumorally. After selection of an adequate dosage for injection from analyses of biodistribution images captured by an IVIS system, PDT was initiated. Three groups were created according to different PDT procedures. In group 1, mice were injected with QDs-RGD intratumorally, and an optical fiber connected to a laser light was inserted directly into the tumor. Irradiation was sustained for 20 min with a laser light (630 nm) at 100 mW/cm(2). In group 2, the laser optical fiber was placed around, and not inserted into, tumors. In group 3, PDT was conducted as in group 1 but without injection of QDs-RGD. After 28 days of observation, tumors on the back of mice in group 1 grew slowly (V/V(0) =3.24±0.70) compared with the control groups, whose tumors grew quickly, and the mean V/V(0) reached 6.08±0.50 (group 2) and 7.25±0.82 (group 3). Histology of tumor tissues showed more necrotic tissues, more inflammatory cells, and less vascular tissue in the PDT group than those in the control groups. These results suggest that QDs-RGD-mediated PDT, with illumination using an optical fiber inserted directly into the tumor, can inhibit the growth of SW1990 tumors with high efficiency in nude mice.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388266/ https://www.dovepress.com/getfile.php?fileID=35858
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13756
      15. Serial :
        13944
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