Browsing by Subject "Polyethylene Glycols"

Now showing 1 - 7 of 7
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    Dual-Enzyme-Loaded Multifunctional Hybrid Nanogel System for Pathological Responsive Ultrasound Imaging and T2-Weighted Magnetic Resonance Imaging.
    (ACS nano, 2015-06) Wang, Xia; Niu, Dechao; Li, Pei; Wu, Qing; Bo, Xiaowan; Liu, Boji; Bao, Song; Su, Teng; Xu, Huixiong; Wang, Qigang
    A dual-enzyme-loaded multifunctional hybrid nanogel probe (SPIO@GCS/acryl/biotin-CAT/SOD-gel, or SGC) has been developed for dual-modality pathological responsive ultrasound (US) imaging and enhanced T2-weighted magnetic resonance (MR) imaging. This probe is composed of functionalized superparamagnetic iron oxide particles, a dual enzyme species (catalase and superoxide dismutase), and a polysaccharide cationic polymer glycol chitosan gel. The dual-modality US/MR imaging capabilities of the hybrid nanogel for responsive US imaging and enhanced T2-weighted MR imaging have been evaluated both in vitro and in vivo. These results show that the hybrid nanogel SGC can exhibit efficient dual-enzyme biocatalysis with pathological species for responsive US imaging. SGC also demonstrates increased accumulation in acidic environments for enhanced T2-weighted MR imaging. Further research on these nanogel systems may lead to the development of more efficient US/MR contrast agents.
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    Injectable laminin-functionalized hydrogel for nucleus pulposus regeneration.
    (Biomaterials, 2013-10) Francisco, Aubrey T; Mancino, Robert J; Bowles, Robby D; Brunger, Jonathan M; Tainter, David M; Chen, Yi-Te; Richardson, William J; Guilak, Farshid; Setton, Lori A
    Cell delivery to the pathological intervertebral disc (IVD) has significant therapeutic potential for enhancing IVD regeneration. The development of injectable biomaterials that retain delivered cells, promote cell survival, and maintain or promote an NP cell phenotype in vivo remains a significant challenge. Previous studies have demonstrated NP cell - laminin interactions in the nucleus pulposus (NP) region of the IVD that promote cell attachment and biosynthesis. These findings suggest that incorporating laminin ligands into carriers for cell delivery may be beneficial for promoting NP cell survival and phenotype. Here, an injectable, laminin-111 functionalized poly(ethylene glycol) (PEG-LM111) hydrogel was developed as a biomaterial carrier for cell delivery to the IVD. We evaluated the mechanical properties of the PEG-LM111 hydrogel, and its ability to retain delivered cells in the IVD space. Gelation occurred in approximately 20 min without an initiator, with dynamic shear moduli in the range of 0.9-1.4 kPa. Primary NP cell retention in cultured IVD explants was significantly higher over 14 days when cells were delivered within a PEG-LM111 carrier, as compared to cells in liquid suspension. Together, these results suggest this injectable laminin-functionalized biomaterial may be an easy to use carrier for delivering cells to the IVD.
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    Large-area nanopatterning of self-assembled monolayers of alkanethiolates by interferometric lithography.
    (Langmuir, 2010-08-17) Adams, J; Tizazu, G; Janusz, Stefan; Brueck, SRJ; Lopez, GP; Leggett, GJ
    We demonstrate that interferometric lithography provides a fast, simple approach to the production of patterns in self-assembled monolayers (SAMs) with high resolution over square centimeter areas. As a proof of principle, two-beam interference patterns, formed using light from a frequency-doubled argon ion laser (244 nm), were used to pattern methyl-terminated SAMs on gold, facilitating the introduction of hydroxyl-terminated adsorbates and yielding patterns of surface free energy with a pitch of ca. 200 nm. The photopatterning of SAMs on Pd has been demonstrated for the first time, with interferometric exposure yielding patterns of surface free energy with similar features sizes to those obtained on gold. Gold nanostructures were formed by exposing SAMs to UV interference patterns and then immersing the samples in an ethanolic solution of mercaptoethylamine, which etched the metal substrate in exposed areas while unoxidized thiols acted as a resist and protected the metal from dissolution. Macroscopically extended gold nanowires were fabricated using single exposures and arrays of 66 nm gold dots at 180 nm centers were formed using orthogonal exposures in a fast, simple process. Exposure of oligo(ethylene glycol)-terminated SAMs to UV light caused photodegradation of the protein-resistant tail groups in a substrate-independent process. In contrast to many protein patterning methods, which utilize multiple steps to control surface binding, this single step process introduced aldehyde functional groups to the SAM surface at exposures as low as 0.3 J cm(-2), significantly less than the exposure required for oxidation of the thiol headgroup. Although interferometric methods rely upon a continuous gradient of exposure, it was possible to fabricate well-defined protein nanostructures by the introduction of aldehyde groups and removal of protein resistance in nanoscopic regions. Macroscopically extended, nanostructured assemblies of streptavidin were formed. Retention of functionality in the patterned materials was demonstrated by binding of biotinylated proteins.
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    ItemOpen Access
    Polyethylene Glycol-conjugated L-asparaginase versus native L-asparaginase in combination with standard agents for children with acute lymphoblastic leukemia in second bone marrow relapse: a Children's Oncology Group Study (POG 8866).
    (Journal of pediatric hematology/oncology, 2011-12) Kurtzberg, Joanne; Asselin, Barbara; Bernstein, Mark; Buchanan, George R; Pollock, Brad H; Camitta, Bruce M

    Background

    Administration of L-asparaginase is limited by hypersensitivity reactions mediated by anti-asparaginase antibodies. To overcome this problem, native Escherichia coli L-asparaginase was conjugated to polyethylene glycol (PEG) to formulate PEG-L-asparaginase, a preparation with decreased immunogenicity and increased circulating half-life. In early trials, PEG-L-asparaginase was tolerated by patients known to be hypersensitive to the native E. coli product.

    Methods

    The Pediatric Oncology Group conducted a phase II, randomized trial to compare the efficacy and toxicity of PEG-L-asparaginase compared with native E. coli asparaginase in children with acute lymphoblastic leukemia in second bone marrow relapse. All patients (n=76) received standard doses of vincristine and prednisone. Nonhypersensitive patients (n=34) were randomized to receive either PEG-L-asparaginase of 2500 IU/m/dose intramuscularly on days 1 and 15 (treatment I) or native E. coli asparaginase of 10,000 IU/m/dose intramuscularly on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 (treatment II). Patients with a clinical history of an allergic reaction to unmodified asparaginase were directly assigned to treatment with PEG-L-asparaginase (n=42). Asparaginase levels and anti-asparaginase antibody titers were monitored in all patients. Response and toxicity were scored using conventional criteria.

    Results

    The complete response rate for the total study population was 41%. There was no difference in complete response between patients randomized to PEG (47%) and native asparaginase (41%). PEG was well tolerated even in patients with prior allergic reactions to native asparaginase. PEG half-life was shorter in patients with prior allergy.

    Conclusions

    PEG asparaginase is a useful agent in patients with allergic reactions to native asparaginase.
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    Safety, tolerability, and mechanisms of antiretroviral activity of pegylated interferon Alfa-2a in HIV-1-monoinfected participants: a phase II clinical trial.
    (J Infect Dis, 2010-06-01) Asmuth, DM; Murphy, RL; Rosenkranz, SL; Lertora, JJ; Kottilil, S; Cramer, Y; Chan, ES; Schooley, RT; Rinaldo, CR; Thielman, N; Li, XD; Wahl, SM; Shore, J; Janik, J; Lempicki, RA; Simpson, Y; Pollard, RB; Clinical Trials Group A5192 Team, AIDS
    BACKGROUND: To our knowledge, the antiviral activity of pegylated interferon alfa-2a has not been studied in participants with untreated human immunodeficiency virus type 1 (HIV-1) infection but without chronic hepatitis C virus (HCV) infection. METHODS: Untreated HIV-1-infected volunteers without HCV infection received 180 microg of pegylated interferon alfa-2a weekly for 12 weeks. Changes in plasma HIV-1 RNA load, CD4(+) T cell counts, pharmacokinetics, pharmacodynamic measurements of 2',5'-oligoadenylate synthetase (OAS) activity, and induction levels of interferon-inducible genes (IFIGs) were measured. Nonparametric statistical analysis was performed. RESULTS: Eleven participants completed 12 weeks of therapy. The median plasma viral load decrease and change in CD4(+) T cell counts at week 12 were 0.61 log(10) copies/mL (90% confidence interval [CI], 0.20-1.18 log(10) copies/mL) and -44 cells/microL (90% CI, -95 to 85 cells/microL), respectively. There was no correlation between plasma viral load decreases and concurrent pegylated interferon plasma concentrations. However, participants with larger increases in OAS level exhibited greater decreases in plasma viral load at weeks 1 and 2 (r = -0.75 [90% CI, -0.93 to -0.28] and r = -0.61 [90% CI, -0.87 to -0.09], respectively; estimated Spearman rank correlation). Participants with higher baseline IFIG levels had smaller week 12 decreases in plasma viral load (0.66 log(10) copies/mL [90% CI, 0.06-0.91 log(10) copies/mL]), whereas those with larger IFIG induction levels exhibited larger decreases in plasma viral load (-0.74 log(10) copies/mL [90% CI, -0.93 to -0.21 log(10) copies/mL]). CONCLUSION: Pegylated interferon alfa-2a was well tolerated and exhibited statistically significant anti-HIV-1 activity in HIV-1-monoinfected patients. The anti-HIV-1 effect correlated with OAS protein levels (weeks 1 and 2) and IFIG induction levels (week 12) but not with pegylated interferon concentrations.
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    Stereocomplexed poly(lactic acid)-poly(ethylene glycol) nanoparticles with dual-emissive boron dyes for tumor accumulation.
    (ACS Nano, 2010-09-28) Kersey, Farrell R; Zhang, Guoqing; Palmer, Gregory M; Dewhirst, Mark W; Fraser, Cassandra L
    Responsive biomaterials play important roles in imaging, diagnostics, and therapeutics. Polymeric nanoparticles (NPs) containing hydrophobic and hydrophilic segments are one class of biomaterial utilized for these purposes. The incorporation of luminescent molecules into NPs adds optical imaging and sensing capability to these vectors. Here we report on the synthesis of dual-emissive, pegylated NPs with "stealth"-like properties, delivered intravenously (IV), for the study of tumor accumulation. The NPs were created by means of stereocomplexation using a methoxy-terminated polyethylene glycol and poly(D-lactide) (mPEG-PDLA) block copolymer combined with iodide-substituted difluoroboron dibenzoylmethane-poly(L-lactide) (BF2dbm(I)PLLA). Boron nanoparticles (BNPs) were fabricated in two different solvent compositions to study the effects on BNP size distribution. The physical and photoluminescent properties of the BNPs were studied in vitro over time to determine stability. Finally, preliminary in vivo results show that stereocomplexed BNPs injected IV are taken up by tumors, an important prerequisite to their use as hypoxia imaging agents in preclinical studies.
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    Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs.
    (Theranostics, 2020-01) Qiao, Li; Hu, Shiqi; Huang, Ke; Su, Teng; Li, Zhenhua; Vandergriff, Adam; Cores, Jhon; Dinh, Phuong-Uyen; Allen, Tyler; Shen, Deliang; Liang, Hongxia; Li, Yongjun; Cheng, Ke
    Cancer is the second leading cause of death worldwide and patients are in urgent need of therapies that can effectively target cancer with minimal off-target side effects. Exosomes are extracellular nano-shuttles that facilitate intercellular communication between cells and organs. It has been established that tumor-derived exosomes contain a similar protein and lipid composition to that of the cells that secrete them, indicating that exosomes might be uniquely employed as carriers for anti-cancer therapeutics. Methods: We isolated exosomes from two cancer cell lines, then co-cultured each type of cancer cells with these two kinds of exosomes and quantified exosome. HT1080 or Hela exosomes were systemically injected to Nude mice bearing a subcutaneous HT1080 tumor to investigate their cancer-homing behavior. Moreover, cancer cell-derived exosomes were engineered to carry Doxil (a common chemotherapy drug), known as D-exo, were used to detect their target and therapeutic efficacy as anti-cancer drugs. Exosome proteome array analysis were used to reveal the mechanism underly this phenomenon. Results: Exosomes derived from cancer cells fuse preferentially with their parent cancer cells, in vitro. Systemically injected tumor-derived exosomes home to their original tumor tissues. Moreover, compared to Doxil alone, the drug-loaded exosomes showed enhanced therapeutic retention in tumor tissues and eradicated them more effectively in nude mice. Exosome proteome array analysis revealed distinct integrin expression patterns, which might shed light on the underlying mechanisms that explain the exosomal cancer-homing behavior. Conclusion: Here we demonstrate that the exosomes' ability to target the parent cancer is a phenomenon that opens up new ways to devise targeted therapies to deliver anti-tumor drugs.