Augmented Therapeutic Potential of Glutaminase Inhibitor CB839 in Glioblastoma Stem Cells Using Gold Nanoparticle Delivery
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.3. Nanoparticle Synthesis
2.4. Loading of CB839 to Gold Nanoparticles (AuR-CB839, R: Cit, ThioPEG, PVP, PVA, PEI)
2.5. Synthesis of Fluorescent PVA Gold Nanoparticles (AuPVA-FITC)
2.6. Cell Cultures
2.7. Colony Formation Assays
2.8. Fluorescent Microscopy
3. Results and Discussion
3.1. Synthesis and Characterization of Au NPs
3.2. Quantification of CB839 Loading
3.3. Physicochemical Characterization of AuPVA-CB839 NPs
3.4. In Vitro Effect of AuPVA-CB839 NPs in GSCs
3.5. Cell Internalization
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Yang, Y.; Hsieh, I.-Y.; Huang, X.; Li, J.; Zhao, W. Glioblastoma Stem-Like Cells: Characteristics, Microenvironment and Therapy. Front. Pharmacol. 2016, 7, 477. [Google Scholar]
- Kahlert, U.D.; Mooney, S.M.; Natsumeda, M.; Steiger, H.-J.; Maciaczyk, J. Targeting cancer stem-like cells in glioblastoma and colorectal cancer through metabolic pathways. Int. J. Cancer 2017, 140, 10–22. [Google Scholar] [CrossRef]
- Harder, B.G.; Blomquist, M.R.; Wang, J.; Kim, A.J.; Woodworth, G.F.; Winkles, J.A.; Loftus, J.C.; Tran, N.L. Developments in Blood-Brain Barrier Penetrance and Drug Repurposing for Improved Treatment of Glioblastoma. Front. Oncol. 2018, 8, 462. [Google Scholar] [CrossRef] [Green Version]
- Garnier, D.; Renoult, O.; Alves-Guerra, M.-C.; Paris, F.; Pecqueur, C. Glioblastoma Stem-Like Cells, Metabolic Strategy to Kill a Challenging Target. Front. Oncol. 2019, 9, 118. [Google Scholar] [CrossRef]
- Cheng, L.; Wu, Q.; Guryanova, O.; Huang, Z.; Huang, Q.; Rich, J.N.; Bao, S. Elevated invasive potential of glioblastoma stem cells. Biochem. Biophys. Res. Commun. 2011, 406, 643–648. [Google Scholar] [CrossRef] [Green Version]
- Singh, S.K.; Clarke, I.D.; Terasaki, M.; Bonn, V.E.; Hawkins, C.; Squire, J.; Dirks, P.B. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003, 63, 5821–5828. [Google Scholar]
- Singleton, D.C.; Dechaume, A.-L.; Murray, P.M.; Katt, W.P.; Baguley, B.C.; Leung, E.Y. Pyruvate anaplerosis is a mechanism of resistance to pharmacological glutaminase inhibition in triple-receptor negative breast cancer. BMC Cancer 2020, 20, 470. [Google Scholar] [CrossRef] [PubMed]
- Zhang, J.; Mao, S.; Guo, Y.; Wu, Y.; Yao, X.; Huang, Y. Inhibition of GLS suppresses proliferation and promotes apoptosis in prostate cancer. Biosci. Rep. 2019, 39. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Seltzer, M.J.; Bennett, B.D.; Joshi, A.D.; Gao, P.; Thomas, A.G.; Ferraris, D.V.; Tsukamoto, T.; Rojas, C.J.; Slusher, B.S.; Rabinowitz, J.D.; et al. Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1. Cancer Res. 2010, 70, 8981–8987. [Google Scholar] [CrossRef] [Green Version]
- Choudhury, M.; Yin, X.; Schaefbauer, K.J.; Kang, J.-H.; Roy, B.; Kottom, T.J.; Limper, A.H.; Leof, E. SIRT7-mediated modulation of glutaminase 1 regulates TGF-β-induced pulmonary fibrosis. FASEB J. 2020, 34, 8920–8940. [Google Scholar] [CrossRef]
- Hoerner, C.R.; Chen, V.J.; Fan, A.C. The ‘Achilles Heel’ of Metabolism in Renal Cell Carcinoma: Glutaminase Inhibition as a Rational Treatment Strategy. Kidney Cancer 2019, 3, 5–29. [Google Scholar] [CrossRef] [Green Version]
- Yu, Y.; Yu, X.; Fan, C.; Wang, H.; Wang, R.; Feng, C.; Guan, H. Targeting glutaminase-mediated glutamine dependence in papillary thyroid cancer. J. Mol. Med. 2018, 96, 777–790. [Google Scholar] [CrossRef] [PubMed]
- Zacharias, N.M.; Baran, N.; Shanmugavelandy, S.S.; Lee, J.; Lujan, J.V.; Dutta, P.; Millward, S.W.; Cai, T.; Wood, C.G.; Piwnica-Worms, D.; et al. Assessing metabolic intervention with a glutaminase inhibitor in real-time by hyperpolarized magnetic resonance in acute myeloid leukemia. Mol. Cancer 2019, 18, 1937–1946. [Google Scholar] [CrossRef] [PubMed]
- Reckzeh, E.S.; Karageorgis, G.; Schwalfenberg, M.; Ceballos, J.; Nowacki, J.; Stroet, M.C.M.; Binici, A.; Knauer, L.; Brand, S.; Choidas, A.; et al. Inhibition of Glucose Transporters and Glutaminase Synergistically Impairs Tumor Cell Growth. Cell Chem. Biol. 2019, 26, 1214–1228. [Google Scholar] [CrossRef]
- De Lartigue, J. Hallmark tumor metabolism becomes a validated therapeutic target. J. Community Support. Oncol. 2018, 16, e47–e52. [Google Scholar] [CrossRef]
- Lukey, M.L.; Cerione, R.A. Starving the Devourer: Cutting Cancer Off from Its Favorite Foods. Cell Chem. Biol. 2019, 26, 1197–1199. [Google Scholar]
- Study of CB-839 in Combination w/Paclitaxel in Patients of African Ancestry and Non-African Ancestry With Advanced TNBC (Clinical Trial ID: NCT03057600). Available online: https://clinicaltrials.gov/ct2/show/NCT03057600 (accessed on 15 February 2021).
- Bennett, M.K.; Gross, M.I.; Bromley, S.D.; Li, J.; Chen, L.; Goyal, B.; Laidig, G.; Stanton, T.F.; Sjogren, E.B.; Calithera Biosciences, Inc. Treatment of Cancer with Heterocyclic Inhibitors of Glutaminase. International Publication No. WO2014/089048 Al, International Application No. PCT/US2013/072830, 12 June 2014. [Google Scholar]
- Gross, M.I.; Demo, S.D.; Dennison, J.B.; Chen, L.; Chernov-Rogan, T.; Goyal, B.; Janes, J.R.; Laidig, G.J.; Lewis, E.R.; Li, J.; et al. Antitumor Activity of the Glutaminase Inhibitor CB-839 in Triple-Negative Breast Cancer. Mol. Cancer Ther. 2014, 13, 890–901. [Google Scholar] [CrossRef] [Green Version]
- Restall, I.J.; Cseh, O.; Richards, L.M.; Pugh, T.J.; Luchman, H.A.; Weiss, S. Brain Tumor Stem Cell Dependence on Glutaminase Reveals a Metabolic Vulnerability through the Amino Acid Deprivation Response Pathway. Cancer Res. 2020, 80, 5478–5490. [Google Scholar] [CrossRef] [PubMed]
- Kahlert, U.D.; Cheng, M.; Koch, K.; Marchionni, L.; Fan, X.; Raabe, E.H.; Maciaczyk, J.; Glunde, K.; Eberhart, C.G. Alterations in cellular metabolome after pharmacological inhibition of Notch in glioblastoma cells. Int. J. Cancer 2016, 138, 1246–1255. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Koch, K.; Hartmann, R.; Tsiampali, J.; Uhlmann, C.; Nickel, A.-C.; He, X.; Kamp, M.; Sabel, M.; Barker, R.; Steiger, H.-J.; et al. A comparative pharmaco-metabolomic study of glutaminase inhibitors in glioma stem-like cells confirms biological effectiveness but reveals differences in target-specificity. Cell Death Discov. 2020, 6, 20. [Google Scholar] [CrossRef] [Green Version]
- Hu, X.; Zhang, Y.; Ding, T.; Liu, J.; Zhao, H. Multifunctional Gold Nanoparticles: A Novel Nanomaterial for Various Medical Applications and Biological Activities. Front. Bioeng. Biotechnol. 2020. [Google Scholar] [CrossRef]
- Maeda, H.; Nakamura, H.; Fang, J. The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv. Drug Deliv. Rev. 2013, 65, 71–79. [Google Scholar] [CrossRef]
- Giesen, B.; Nickel, A.-C.; Garzón-Manjón, A.; Vargas-Toscano, A.; Scheu, C.; Kahlert, U.D.; Janiak, C. Influence of synthesis methods on the internalization of fluorescent gold nanoparticles into glioblastoma stem-like cells. J. Inorg. Biochem. 2020, 203, 110952. [Google Scholar] [CrossRef] [PubMed]
- Zimmermann, S.C.; Wolf, E.F.; Luu, A.; Thomas, A.G.; Stathis, M.; Poore, B.; Nguyen, C.; Le, A.; Rojas, C.; Slusher, B.S.; et al. Allosteric Glutaminase Inhibitors Based on a 1,4-Di(5-amino-1,3,4-thiadiazol-2-yl)butane Scaffold. ACS Med. Chem. Lett. 2016, 7, 520–524. [Google Scholar] [CrossRef] [PubMed]
- Mao, W.; Kim, H.S.; Son, Y.J.; Kim, S.R.; Yoo, H.S. Doxorubicin encapsulated clicked gold nanoparticle clusters exhibiting tumor-specific disassembly for enhanced tumor localization and computerized tomographic imaging. J. Control. Release 2018, 269, 52–62. [Google Scholar] [CrossRef]
- Ruan, S.; Yuan, M.; Zhang, L.; Hu, G.; Chen, J.; Cun, X.; Zhang, Q.; Yang, Y.; He, Q.; Gao, H. Tumor microenvironment sensitive doxorubicin delivery and release to glioma using angiopep-2 decorated gold nanoparticles. Biomaterials 2015, 37, 425–435. [Google Scholar] [CrossRef] [PubMed]
- Fu, Y.; Feng, Q.; Chen, Y.; Shen, Y.; Su, Q.; Zhang, Y.; Zhou, X.; Cheng, Y. Comparison of Two Approaches for the Attachment of a Drug to Gold Nanoparticles and Their Anticancer Activities. Mol. Pharm. 2016, 13, 3308–3317. [Google Scholar] [CrossRef]
- Zhao, H.; Lin, Z.Y.; Yildirimer, L.; Dhinakar, A.; Zhao, X.; Wu, J. Polymer-based nanoparticles for protein delivery: Design, strategies and applications. J. Mater. Chem. B 2016, 4, 4060–4071. [Google Scholar] [CrossRef]
- Qin, X.; Li, Y. Strategies to Design and Synthesize Polymer-Based Stimuli-Responsive Drug-Delivery Nanosystems. ChemBioChem 2020, 21, 1236–1253. [Google Scholar] [CrossRef]
- Negron, K.; Khalasawi, N.; Lu, B.; Ho, C.-Y.; Lee, J.; Shenoy, S.; Mao, H.-Q.; Wang, T.-H.; Hanes, J.; Suk, J.S. Widespread gene transfer to malignant gliomas with In vitro-to-In vivo correlation. J. Control. Release 2019, 303, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.M.; Mhawech-Fauceglia, P.; Lee, N.; Parsanian, L.C.; Lin, Y.G.; Gayther, S.A.; Lawrenson, K. A three-dimensional microenvironment alters protein expression and chemosensitivity of epithelial ovarian cancer cells in vitro. Lab. Investig. 2013, 93, 528–542. [Google Scholar]
- Kang, M.S.; Lee, S.Y.; Kim, K.S.; Han, D.-W. State of the Art Biocompatible Gold Nanoparticles for Cancer Theragnosis. Pharmaceutics 2020, 12, 701. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.D.; Wu, D.; Shen, X.; Liu, P.X.; Yang, N.; Zhao, B.; Zhang, H.; Sun, Y.M.; Zhang, L.A.; Fan, F.Y. Size-dependent in vivo toxicity of PEG-coated gold nanoparticles. Int. J. Nanomed. 2011, 6, 2071–2081. [Google Scholar] [CrossRef] [Green Version]
- Paradossi, G.; Cavalieri, F.; Chiessi, E.; Spagnoli, C.; Cowman, M.K. Poly(vinyl alcohol) as versatile biomaterial for potential biomedical applications. J. Mater. Sci. Mater. Med. 2003, 14, 687–691. [Google Scholar] [CrossRef] [PubMed]
- Acharya, A.P.; Chan, S.Y.W.; Little, S.R.; University of Pittsburgh of the Commonwealth System of Higher Education. Compositions and Methods for Administering a YAP1/WWRT1 Inhibiting Composition and a GLS1 Inhibiting Composition. International Publication No. WO2019/104038 Al, International Application No. PCT/US2018/062013, 31 May 2019. [Google Scholar]
- Ruan, B.; Ruan, J. Faming Zhuanli Shenqing. Liposome containing glutamine metabolism inhibitor and pharmaceutical composition and use thereof. Patent No. CN107714650, 23 February 2018. [Google Scholar]
- Adewale, O.B.; Davids, H.; Cairncross, L.; Roux, S. Toxicological Behavior of Gold Nanoparticles on Various Models: Influence of Physicochemical Properties and Other Factors. Int. J. Toxicol. 2019, 38, 357–384. [Google Scholar] [CrossRef] [PubMed]
- Sanabria, N.M.; Gulumian, M. The presence of residual gold nanoparticles in samples interferes with the RT-qPCR assay used for gene expression profiling. J. Nanobiotechnol. 2017, 15, 1–26. [Google Scholar] [CrossRef] [Green Version]
- Ponti, J.; Kinsner-Ovaskainen, A.; Norlen, H.; Altmeyer, S.; Cristina, A.; Bogni, A. Interlaboratory Comparison Study of the Colony Forming Efficiency Assay for Assessing Cytotoxicity of Nanomaterials. EUR—Scientific and Technical Research Reports; Report No. 978-92-79-44677-1; Publications Office of the European Union: Luxembourg, 2014. [Google Scholar]
- Ernst Ruska-Centre for Microscopy and Spectroscopy with Electrons. FEI Tecnai G2 F20. J. Large-Scale Res. Facil. 2016, 2, 77. [Google Scholar] [CrossRef] [Green Version]
- Kahlert, U.D.; Suwala, A.K.; Raabe, E.H.; Siebzehnrubl, F.A.; Suarez, M.J.; Orr, B.A.; Bar, E.E.; Maciaczyk, J.; Eberhart, C.G. ZEB1 promotes invasion in human fetal neural stem cells and hypoxic glioma neurospheres. Brain Pathol. 2015, 25, 724–732. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liston, D.R.; Davis, M. Clinically Relevant Concentrations of Anticancer Drugs: A Guide for Nonclinical Studies. Clin. Cancer Res. 2017, 23, 3489–3498. [Google Scholar] [CrossRef] [Green Version]
- Tsiampali, J.; Neumann, S.; Giesen, B.; Koch, K.; Maciaczyk, D.; Janiak, C.; Hänggi, D.; Maciaczyk, J. Enzymatic Activity of CD73 Modulates Invasion of Gliomas via Epithelial-Mesenchymal Transition-Like Reprogramming. Pharmaceutics 2020, 13, 378. [Google Scholar] [CrossRef]
- Turkevich, J.; Stevenson, P.C.; Hillier, J. A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss. Faraday Soc. 1951, 11, 55–75. [Google Scholar] [CrossRef]
- Zhang, H.; Ren, P.; Yang, F.; Chen, J.; Wang, C.; Zhou, Y.; Fu, J. Biomimetic epidermal sensors assembled from polydopamine-modified reduced graphene oxide/polyvinyl alcohol hydrogels for the real-time monitoring of human motions. J. Mater. Chem. B 2020, 8, 10549. [Google Scholar] [CrossRef]
- McHugh, K.; Jing, L.; Severt, S.Y.; Cruz, M.; Sarmadi, M.; Jayawardena, H.S.N.; Perkinson, C.F.; Larusson, F.; Rose, S.; Tomasic, S.; et al. Biocompatible near- infrared quantum dots delivered to the skin by microneedle patches record vaccination. Sci. Transl. Med. 2019, 11, e7162. [Google Scholar] [CrossRef] [PubMed]
- Huang, Q.; Stalnecker, C.; Zhang, C.; McDermott, L.A.; Iyer, P.; O’Neill, J.; Reimer, S.; Cerione, R.A.; Katt, W.P. Characterization of the interactions of potent allosteric inhibitors with glutaminase C, a key enzyme in cancer cell glutamine metabolism. J. Biol. Chem. 2018, 293, 3535–3545. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cheng, X.; Tian, X.; Wu, A.; Li, J.; Tian, J.; Chong, Y.; Chai, Z.; Zhao, Y.; Chen, C.; Ge, C. Protein Corona Influences Cellular Uptake of Gold Nanoparticles by Phagocytic; Nonphagocytic Cells in a Size-Dependent Manner. ACS Appl. Mater. Interfaces 2015, 7, 20568–20575. [Google Scholar] [CrossRef] [PubMed]
- Larsson, P.; Engqvist, H.; Biermann, J.; Rönnerman, E.W.; Forssell-Aronsson, E.; Kovács, A.; Karlsson, P.; Helou, K.; Parris, T.Z. Optimization of cell viability assays to improve replicability and reproducibility of cancer drug sensitivity screens. Sci. Rep. 2020, 10, 5798. [Google Scholar] [CrossRef] [PubMed]
- Elgogary, A.; Xu, Q.; Poore, B.; Alt, J.; Zimmermann, S.C.; Zhao, L.; Fu, J.; Chen, B.; Xia, S.; Liu, Y.; et al. Combination therapy with BPTES nanoparticles and metformin targets the metabolic heterogeneity of pancreatic cancer. Proc. Natl. Acad. Sci. USA 2016, 113, e5328–e5336. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fischer, I.; Nickel, A.-C.; Qin, N.; Taban, K.; Pauck, D.; Steiger, H.-J.; Kamp, M.; Muhammad, S.; Hänggi, D.; Fritsche, E.; et al. Different Calculation Strategies Are Congruent in Determining Chemotherapy Resistance of Brain Tumors In Vitro. Cells 2020, 9, 2689. [Google Scholar] [CrossRef]
- Khadka, S.; Arthur, K.; Washington, M.; Barekatain, Y.; Ackroyd, J.; Behr, E.; Suriyamongkol, P.; Lin, Y.-H.; Crowley, K.; Pham, C.D.; et al. Impaired Anaplerosis Is a Major Contributor to Glycolysis Inhibitor Toxicity in Glioma. PREPRINT 2020. [Google Scholar] [CrossRef]
- Sokolova, V.; Mekky, G.; Van der Meer, S.B.; Seeds, M.C.; Atala, A.J.; Epple, M. Transport of ultrasmall gold nanoparticles (2 nm) across the blood-brain barrier in a six-cell brain spheroid model. Sci. Rep. 2020, 10, 18033. [Google Scholar] [CrossRef]
- Khongkow, M.; Yata, T.; Boonrungsiman, S.; Ruktanonchai, U.R.; Graham, D.; Namdee, K. Surface modification of gold nanoparticles with neuron-targeted exosome for enhanced blood-brain barrier penetration. Sci. Rep. 2019, 9, 8278. [Google Scholar] [CrossRef] [PubMed]
- Cheng, Y.; Dai, Q.; Morshed, R.A.; Fan, X.; Wegscheid, M.L.; Wainwright, D.A.; Han, Y.; Zhang, L.; Auffinger, B.; Tobias, A.L.; et al. Blood-brain barrier permeable gold nanoparticles: An efficient delivery plat-form for enhanced malignant glioma therapy and imaging. Small 2014, 10, 5137–5150. [Google Scholar] [CrossRef]
- Sheleg, S.V.; Korotkevich, E.A.; Zhavrid, E.A.; Muravskaya, G.V.; Smeyanovich, A.F.; Shanko, Y.G.; Yurkshtovich, T.L.; Bychkovsky, P.B.; Belyaev, S.A. Local chemotherapy with cisplatin-depot for glioblastoma multiforme. J. Neurooncol. 2002, 60, 53–59. [Google Scholar] [CrossRef] [PubMed]
- Nam, L.; Coll, C.; Erthal, L.C.S.; de la Torre, C.; Serrano, D.; Martínez-Máñez, R.; Santos-Martínez, M.J.; Ruiz-Hernández, E. Drug Delivery Nanosystems for the Localized Treatment of Glioblastoma Multiforme. Materials 2018, 11, 779. [Google Scholar] [CrossRef] [Green Version]
- Lenting, K.; Verhaak, R.; Ter Laan, M.; Wesseling, P.; Leenders, W. Glioma: Experimental models and reality. Acta Neuropathol. 2017, 133, 263–282. [Google Scholar] [CrossRef] [Green Version]
- Huszthy, P.C.; Daphu, I.; Niclou, S.P.; Stieber, D.; Nigro, J.M.; Sakariassen, P.; Miletic, H.; Thorsen, F.; Bjerkvig, R. In vivo models of primary brain tumors: Pitfalls and perspectives. Neuro. Oncol. 2012, 14, 979–993. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Robertson, F.L.; Marqués-Torrejón, M.A.; Morrison, G.M.; Pollard, S.M. Experimental models and tools to tackle glioblastoma. Dis. Models Mech. 2019, 12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Upadhyay, U.M.; Tyler, B.; Patta, Y.; Wicks, R.; Spencer, K.; Scott, A.; Masi, B.; Hwang, L.; Grossman, R.; Cima, M.; et al. Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain. Proc. Natl. Acad. Sci. USA 2014, 111, 16071–16076. [Google Scholar] [CrossRef] [Green Version]
- Semenkow, S.; Li, S.; Kahlert, U.D.; Raabe, E.H.; Xu, J.; Arnold, A.; Janowski, M.; Oh, B.C.; Brandacher, G.; Bulte, J.W.M.; et al. An immunocompetent mouse model of human glioblastoma. Oncotarget 2017, 8, 61072–61082. [Google Scholar] [CrossRef] [Green Version]
- Lan, X.; Kedziorek, D.A.; Chu, C.; Jablonska, A.; Li, S.; Kai, M.; Liang, Y.; Janowski, M.; Walczak, P. Modeling human pediatric and adult gliomas in immunocompetent mice through costimulatory blockade. Oncoimmunology 2020, 9, 1776577. [Google Scholar] [CrossRef] [PubMed]
- Wei, S.-C.; Hsu, P.-H.; Lee, Y.-F.; Lin, Y.-W.; Huang, C.-C. Selective Detection of Iodide and Cyanide Anions Using Gold-Nanoparticle-Based Fluorescent Probes. ACS Appl. Mater. Interfaces 2012, 4, 2652–2658. [Google Scholar] [CrossRef]
- Zhao, P.; Li, N.; Astruc, D. State of the art in gold nanoparticle synthesis. Coord. Chem. Rev. 2013, 257, 638–665. [Google Scholar] [CrossRef]
- Boles, M.; Ling, D.; Hyeon, T.; Talapin, D.V. The surface science of nanocrystals. Nat. Mater. 2016, 15, 141–153. [Google Scholar] [CrossRef] [PubMed]
- Xue, Y.; Li, X.; Li, H.; Zhang, W. Quantifying thiol–gold interactions towards the efficient strength control. Nat. Commun. 2014, 5, 4348. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, S.; Wang, X.; Zhang, Z.; Chen, L. Highly sensitive fluorescence detection of copper ion based on its catalytic oxidation to cysteine indicated by fluorescein isothiocyanate functionalized gold nanoparticles. Colloids Surf. A Physicochem. Eng. Asp. 2015, 468, 333–338. [Google Scholar] [CrossRef]
- Donahue, N.D.; Acar, H.; Wilhelm, S. Concepts of nanoparticle cellular uptake, intracellular trafficking, and kinetics in nanomedicine. Adv. Drug Deliv. Rev. 2019, 143, 68–96. [Google Scholar] [CrossRef] [PubMed]
Au NPs | Drug Loading Efficiency (%) |
---|---|
AuCit | 8 |
AuThioPEG | 4 |
AuPVA | 12 |
AuPVP | 0 |
AuPEI | 1 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Giesen, B.; Nickel, A.-C.; Barthel, J.; Kahlert, U.D.; Janiak, C. Augmented Therapeutic Potential of Glutaminase Inhibitor CB839 in Glioblastoma Stem Cells Using Gold Nanoparticle Delivery. Pharmaceutics 2021, 13, 295. https://doi.org/10.3390/pharmaceutics13020295
Giesen B, Nickel A-C, Barthel J, Kahlert UD, Janiak C. Augmented Therapeutic Potential of Glutaminase Inhibitor CB839 in Glioblastoma Stem Cells Using Gold Nanoparticle Delivery. Pharmaceutics. 2021; 13(2):295. https://doi.org/10.3390/pharmaceutics13020295
Chicago/Turabian StyleGiesen, Beatriz, Ann-Christin Nickel, Juri Barthel, Ulf Dietrich Kahlert, and Christoph Janiak. 2021. "Augmented Therapeutic Potential of Glutaminase Inhibitor CB839 in Glioblastoma Stem Cells Using Gold Nanoparticle Delivery" Pharmaceutics 13, no. 2: 295. https://doi.org/10.3390/pharmaceutics13020295