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F H Wang, K Bae, Z W Huang, J M Xue
For obtaining high-resolution macroscopical anatomical information and high sensitivity microscopical optical signals, it is highly desirable to develop dual-modality magnetic resonance imaging (MRI) and fluorescent probes in medical imaging simultaneously. In this study, Gd2 O3 nanoparticles were modified with two-photon graphene quantum dots (GQD), integrating a magnetic resonance imaging (MRI) contrast agent with two-photon imaging functionality into one nanoprobe. A photoluminescence study indicated that the GQD modification process integrated MRI properties with both one-photon and two-photon imaging properties...
March 12, 2018: Nanoscale
Yu Cheng, Xiaoxiao Tan, Jinping Wang, Yidan Wang, Yilin Song, Qing You, Qi Sun, Li Liu, Siyu Wang, Fengping Tan, Jiao Li, Nan Li
Recently, ultrasmall gadolinium oxide (Gd2 O3 ) nanoparticles with high longitudinal relaxation rate have received enormous attention. However, it can't be concentrated in tumor site through intravenous administration due to its ultrasmall size. In this project, we coated ultrasmall Gd2 O3 nanoparticles with a near-infrared (NIR) light-absorbing polymer polypyrrole (PPy), modifying with hyaluronic acid (HA) and loaded aluminum phthalocyanine (AlPc), the Gd2 O3 @PPy/AlPc-HA nanoparticles could be used for fluorescence (FL)/magnetic resonance (MR)/photoacoustic (PA) imaging guided as well as remotely controlled PTT/PDT combined anti-tumor therapy...
March 8, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Miriam Palacios, Ricardo Tampe, Miguel Del Campo, Ta-Ying Zhong, Mercedes N López, Flavio Salazar-Onfray, María Inés Becker
Conjugation to carrier proteins is a way to improve the immunogenicity of peptides. Such is the case for peptides mimicking carbohydrate tumor-associated antigens in cancer vaccine development. The most used protein for this purpose is the keyhole limpet hemocyanin (KLH) from Megathura crenulata. Its limited bioavailability has prompted interest in finding new candidates; nevertheless, it is not known whether other hemocyanins might be equally efficient as carrier of carbohydrate peptide mimotopes to promotes anti-tumor responses...
February 27, 2018: European Journal of Medicinal Chemistry
Shailja Kumar, Virendra Kumar Meena, Puja Panwar Hazari, Surinder Kumar Sharma, Rakesh Kumar Sharma
We report here, reverse micelle mediated synthesis of multifunctional dextran (dex) coated Gd2 O3 nanoparticles (NPs) carrying rose bengal (RB) dye for magnetic resonance and optical imaging. The diameter of these RB attached dex coated Gd2 O3 NPs (Gd-dex-RB NPs) was found to be ~17 nm as measured by TEM. NMR line broadening effect on the surrounding water protons affirmed the paramagnetic nature of these NPs. Optical properties of Gd-dex-RB NPs were validated by UV-Vis and fluorescence spectroscopy. Time dependent release profile of RB from NPs at two different pH of 7...
March 6, 2018: European Journal of Pharmaceutical Sciences
Shima Gholizadeh, Emmy M Dolman, Rebecca Wieriks, Rolf W Sparidans, Wim E Hennink, Robbert J Kok
PURPOSE: Sepantronium bromide (YM155) is a hydrophilic quaternary compound that cannot be administered orally due to its low oral bioavailability; it is furthermore rapidly eliminated via the kidneys. The current study aims at improving the pharmacokinetic profile of YM155 by its formulation in immunoliposomes that can achieve its enhanced delivery into tumor tissue and facilitate uptake in neuroblastoma cancer cells. METHODS: PEGylated YM155 loaded liposomes composed of DPPC, cholesterol and DSPE-PEG2000 were prepared via passive film-hydration and extrusion method...
March 7, 2018: Pharmaceutical Research
Sushil Kumar Ranjan, Abhishek Kumar Soni, Vineet Kumar Rai
Frequency up-conversion (UC) emission from the Nd3+ -Yb3+ /Nd3+ -Yb3+ -Li+ co-doped gadolinium oxide (Gd2 O3 ) phosphors prepared by the solution combustion technique in the visible range have been studied by using 980 nm near infrared (NIR) laser diode excitation. The crystalline structure and formation of the cubic phase has been confirmed with the help of X-ray diffraction (XRD) studies. XRD peak shifts have been found towards the lower diffraction angle side in the case of the Nd3+ -Yb3+ -Li+ co-doped phosphors...
March 2, 2018: Luminescence: the Journal of Biological and Chemical Luminescence
G Velkos, D S Krylov, K Kirkpatrick, X Liu, L Spree, A U B Wolter, B Büchner, H C Dorn, A A Popov
Magnetic properties of the azafullerene Gd2 @C79 N are studied by SQUID magnetometry. The effective exchange coupling constant jGd,e between the Gd spins and the spin of unpaired electron residing on the single-electron Gd-Gd bond is determined to be 170 ± 10 cm-1 . Low temperature AC measurements revealed field-induced millisecond-long relaxation of magnetization.
March 2, 2018: Chemical Communications: Chem Comm
Austin Jack Ryan, Lucy E Darago, Sree Ganesh Balasubramini, Guo P Chen, Joseph W Ziller, Filipp Furche, Jeffrey R Long, William J Evans
A new series of Ln2+ complexes has been synthesized that overturns two previous generalizations in rare-earth metal reduction chemistry: that amide ligands do not form isolable complexes of the highly-reducing non-traditional Ln2+ ions and that yttrium is a good model for the late lanthanides in these reductive reactions. Reduction of Ln(NR2)3 (R = SiMe3) complexes in THF under Ar with M = K or Rb in the presence of 2.2.2-cryptand (crypt) forms crystallographically-characterizable [M(crypt)][Ln(NR2)3] complexes not only for the traditional Tm2+ ion and the configurational crossover ions, Nd2+ and Dy2+, but also for the non-traditional Gd2+, Tb2+, Ho2+, and Er2+ ions...
February 28, 2018: Chemistry: a European Journal
Liping Tong, Katsuhiko Saito, Qixin Guo, Han Zhou, Xingmei Guo, Tongxiang Fan, Di Zhang
A correlation function between the Raman intensities and the nearest-neighbor mean-square relative displacement (MSRD) [Formula: see text] of local Bi-O bonds is successfully established based on x-ray absorption fine structure (XAFS) and temperature-dependent Raman spectra in the temperature range 77-300 K in amorphous and crystalline Gd2.95 Yb0.02 Bi0.02 Er0.01 Ga5 O12 . The structural symmetries of Gd2.95 Yb0.02 Bi0.02 Er0.01 Ga5 O12 are described by using [Formula: see text] of local Bi-O bonds. More importantly, Gd2...
February 23, 2018: Journal of Physics. Condensed Matter: An Institute of Physics Journal
Xiaoling Wang, Johannes E McKay, Bimala Lama, Johan van Tol, Tinghui Li, Kyle Kirkpatrick, Zhehong Gan, Stephen Hill, Joanna R Long, Harry C Dorn
We show increased dynamic nuclear polarization by adding a low dosage of a S = 15/2 Gd based endohedral metallofullerene (EMF) to DNP samples. By adding 60 μM Gd2 @C79 N, the nuclear polarization of1 H and13 C spins from 40 mM 4-oxo-TEMPO increases by approximately 40% and 50%, respectively, at 5 T and 1.2 K. Electron-electron double resonance (ELDOR) measurements show that the high spin EMF shortens the electron relaxation times and increases electron spectral diffusion leading to the increased DNP enhancement...
February 19, 2018: Chemical Communications: Chem Comm
Weihong Zhu, Xinzhan Mao, Wanchun Wang, You Chen, Ding Li, Hui Li, Pengcheng Dou
Cisplatin is an effective chemotherapeutic agent for osteosarcoma (OS) and has been shown to induce endoplasmic reticulum (ER) stress-associated apoptosis in human cancer cells. Ganglioside GD2-specific antibodies can inhibit tumor cell viability without involvement of the immune system. A recent study has shown that antiGD2 monoclonal antibody (mAb) 14G2a effectively inhibits the viability and invasiveness of human OS cells. In this study, we explored the effect of anti-GD2 mAb and cisplatin alone and in combination on ER stress-associated apoptosis in osteosarcoma cells...
February 1, 2018: Die Pharmazie
Taiji Iwasawa, Pu Zhang, Yuki Ohkawa, Hiroyuki Momota, Toshihiko Wakabayashi, Yuhsuke Ohmi, Robiul H Bhuiyan, Keiko Furukawa, Koichi Furukawa
Sialic acid-containing glycosphingolipids, gangliosides, are considered as cancer associated antigens in neuro-ectoderm-derived tumors such as melanomas and neuroblastomas. In particular, gangliosides GD3 and GD2 are expressed in human gliomas. It has been reported that their expression levels increase along with increased malignant properties. However, the implication of GD3/GD2 in human glioma cells has never been clarified, at least to the best of our knowledge. In this study, we introduced the cDNA of GD3 synthase (GD3S)(ST8SIA1) into a glioma cell line, U-251MG, that expresses neither GD3 nor GD2, thereby establishing transfectant cells U-251MG-GD3S(+) expressing high levels of GD3 and GD2 on the cell surface...
February 7, 2018: International Journal of Oncology
Lindi Chen, Arman Esfandiari, William Reaves, Annette Vu, Michael D Hogarty, John Lunec, Deborah A Tweddle
Cell lines established from the TH-MYCN transgenic murine model of neuroblastoma are a valuable preclinical, immunocompetent, syngeneic model of neuroblastoma, for which knowledge of their p53 pathway status is important. In this study, the Trp53 status and functional response to Nutlin-3 and ionising radiation (IR) were determined in 6 adherent TH-MYCN transgenic cell lines using Sanger sequencing, western blot analysis and flow cytometry. Sensitivity to structurally diverse MDM2 inhibitors (Nutlin-3, MI-63, RG7388 and NDD0005) was determined using XTT proliferation assays...
January 31, 2018: International Journal of Oncology
Yadong Xu, Alvaro Goyanes, Yuwei Wang, Andrew J Weston, Po-Wah So, Carlos F G C Geraldes, Andrew M Fogg, Abdul W Basit, Gareth R Williams
The potential of the layered gadolinium hydroxide (LGdH) [Gd2(OH)5]Cl·yH2O (LGdH-Cl) for simultaneous drug delivery and magnetic resonance imaging was explored in this work. Three non-steroidal anti-inflammatory drugs (diclofenac [dic], ibuprofen [ibu], and naproxen [nap]) were intercalated into LGdH-Cl for the first time, using three different routes (ion exchange intercalation, coprecipitation, and exfoliation-self-assembly). X-ray diffraction, elemental microanalysis and IR spectroscopy confirmed successful incorporation of the drug into the interlayer spaces of the LGdH in all cases...
January 22, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Kiraz Ceylan, Luciana J Jahns, Bjoern N Lode, Karoline Ehlert, Silke Kietz, Sascha Troschke-Meurer, Nikolai Siebert, Holger N Lode
BACKGROUND: The monoclonal anti-GD2 antibody ch14.18/CHO in combination with IL-2 is active and effective in high-risk neuroblastoma (NB) patients. Here, we investigated the inflammatory response and treatment tolerance of long-term infusion (LTI) of ch14.18/CHO (10 × 10 mg/m2 ; 24 hr) in combination with subcutaneous (s.c.) IL-2 in a single center program. METHODS: Fifty-three NB patients received up to six cycles of 100 mg/m2 ch14.18/CHO (d8-18, where d represents day(s)) as LTI combined with 6 × 106 IU/m2 s...
January 19, 2018: Pediatric Blood & Cancer
Rosa Nguyen, Jim Houston, Wing K Chan, David Finkelstein, Michael A Dyer
Although anti-disialoganglioside (GD2) antibodies are successfully used for neuroblastoma therapy, a third of patients with neuroblastoma experience treatment failure or serious toxicity. Various strategies have been employed in the clinic to improve antibody-dependent cell-mediated cytotoxicity (ADCC), such as the addition of interleukin (IL)-2 to enhance natural killer (NK) cell function, adoptive transfer of allogeneic NK cells to exploit immune surveillance, and retinoid-induced differentiation therapy...
January 11, 2018: Cancer Immunology, Immunotherapy: CII
Nicola Mitwasi, Anja Feldmann, Ralf Bergmann, Nicole Berndt, Claudia Arndt, Stefanie Koristka, Alexandra Kegler, Justyna Jureczek, Anja Hoffmann, Armin Ehninger, Marc Cartellieri, Susann Albert, Claudia Rossig, Gerhard Ehninger, Jens Pietzsch, Jörg Steinbach, Michael Bachmann
As the expression of a tumor associated antigen (TAA) is commonly not restricted to tumor cells, adoptively transferred T cells modified to express a conventional chimeric antigen receptor (CAR) might not only destroy the tumor cells but also attack target-positive healthy tissues. Furthermore, CAR T cells in patients with large tumor bulks will unpredictably proliferate and put the patients at high risk of adverse side effects including cytokine storms and tumor lysis syndrome. To overcome these problems, we previously established a modular CAR technology termed UniCAR: UniCAR T cells can repeatedly be turned on and off via dosing of a target module (TM)...
December 12, 2017: Oncotarget
Anna Capsomidis, Gabriel Benthall, Heleen H Van Acker, Jonathan Fisher, Anne M Kramer, Zarah Abeln, Yvonne Majani, Talia Gileadi, Rebecca Wallace, Kenth Gustafsson, Barry Flutter, John Anderson
Gamma delta T (γδT) lymphocytes are primed for rapid function, including cytotoxicity toward cancer cells, and are a component of the immediate stress response. Following activation, they can function as professional antigen-presenting cells. Chimeric antigen receptors (CARs) work by focusing T cell function on defined cell surface tumor antigens and provide essential costimulation for robust activation. Given the natural tropism of γδT cells for the tumor microenvironment, we hypothesized that their transduction with CARs might enhance cytotoxicity while retaining their ability to migrate to tumor and act as antigen-presenting cells to prolong the intratumoral immune response...
December 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
Jiayi Yu, Xiaowen Wu, Junya Yan, Huan Yu, Longwen Xu, Zhihong Chi, Xinan Sheng, Lu Si, Chuanliang Cui, Jie Dai, Meng Ma, Tianxiao Xu, Yan Kong, Jun Guo
BACKGROUND: Chimeric antigen receptor (CAR)-engineered T cells have demonstrated promising clinical efficacy in patients with B cell lymphoma. However, the application of CAR-T cell therapy in the treatment of other solid tumors has been limited. We incorporated 4-1BB into the anti-GD2 CAR-T cells to test their cytotoxicity in melanoma in vitro and in vivo. Moreover, we reported the expression of ganglioside GD2 in non-Caucasian melanoma populations for the first time, thus providing a basis for future clinical research...
January 3, 2018: Journal of Hematology & Oncology
K Greenwood, J H Foster
Dinutuximab is a monoclonal antibody targeted at disialoganglioside (GD2), a tumor-associated antigen widely expressed in human neuroblastoma cells. The incorporation of dinutuximab into standard treatment regimens for patients with high-risk neuroblastoma has changed the landscape of neuroblastoma therapy. Dinutuximab has shown to be effective in prolonging survival for patients receiving standard multimodal treatment regimens and has now become standard of care during the final phase of treatment. More recently, it has also shown promising efficacy and tolerability in patients with relapsed or progressive neuroblastoma...
September 2017: Drugs of Today
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