You have accessJournal of UrologyBladder Cancer: Basic Research (I)1 Apr 2013595 GOLD NANOPARTICLE CAN SERVE AS AGENTS FOR IMMUNOMODULATION IN MURINE BLADDER TUMOR MODELS BY CAUSING THE CONFORMATIONAL CHANGES AND ATTENUATING THE BIOLOGICAL FUNCTION OF TGF-β1 PROTEIN Yuh-Shyan Tsai, Yu-Hung Chen, Pai-Chiao Cheng, Hsin-Tzu Tsai, Ai-Li Shiau, Tzong-Shin Tzai, and Chao-Liang Wu Yuh-Shyan TsaiYuh-Shyan Tsai Tainan, Taiwan More articles by this author , Yu-Hung ChenYu-Hung Chen Tainan, Taiwan More articles by this author , Pai-Chiao ChengPai-Chiao Cheng Tainan, Taiwan More articles by this author , Hsin-Tzu TsaiHsin-Tzu Tsai Tainan, Taiwan More articles by this author , Ai-Li ShiauAi-Li Shiau Tainan, Taiwan More articles by this author , Tzong-Shin TzaiTzong-Shin Tzai Tainan, Taiwan More articles by this author , and Chao-Liang WuChao-Liang Wu Tainan, Taiwan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1991AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Gold nanoparticles (AuNPs) have been widely used as carriers due to their great bio-compatibility and unique physical properties and potentially as therapeutic agents for inactivating vascular endothelial growth factor (VEGF). Like VEGF, transforming growth factor-beta 1 (TGF-β1) is a member of the cysteine-knot structural superfamily and plays a pivotal role in many diseases and is known as an immunosuppressive agent. The study is aimed to investigate whether AuNPs can serve as an intratumoral immunomodulation and its mechanism. METHODS Murine bladder tumor-2 cells (MBT2), normal murine mammary gland cells (NMuMg), C3H/HeN and NOD-SCID mice were used for in vitro and in vivo studies, including cell growth assay and tumor growth assay. X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy were used for exploring the mechanism of AuNP-TGFβ1 conjugation. RESULTS The results reflected strong interactions between TGF-β1 and the surface of AuNPs when incubated with serum-containing medium, demonstrating a time- and dose-dependent pattern from both immunoassays and Western blotting studies. Compared with other serum proteins which also can bind to AuNP surface, AuNP-TGFβ1 conjugate is a thermodynamically favored compound. Epithelial cells underwent epithelial-mesenchymal transition (EMT) upon treatment with TGF-β1; however, treatment with AuNPs reversed this effect, as detected by cell morphology and expression levels of EMT markers. TGF-β1 was found to bind to AuNPs through S-Au bonds by X-ray photoelectron spectroscopy. To understand why the activity of TGF-β1 was attenuated after conjugating to AuNPs, Fourier transform infrared spectroscopy was employed to analyze the conformational changes of TGF-β1 on the surface of AuNPs. The results indicated that TGF-β1 underwent significant conformational changes at both secondary and tertiary structural levels after conjugation to the AuNP surface, resulting in the deactivation of TGF-β1 protein. An in vivo experiment also showed that addition of AuNPs attenuated the growth of TGF-β1-secreting murine bladder tumor-2 cells in syngeneic C3H/HeN mice, but not in immunocompromised NOD-SCID mice, and this was associated with an increase in the number of tumor-infiltrating CD4+ and CD8+ T lymphocytes, and a decrease in the number of intrasplenic Foxp3(+) lymphocytes. CONCLUSIONS AuNPs may be a promising agent for modulating tumor immunity through inhibiting immunosuppressive TGF-β1 signaling. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e243 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yuh-Shyan Tsai Tainan, Taiwan More articles by this author Yu-Hung Chen Tainan, Taiwan More articles by this author Pai-Chiao Cheng Tainan, Taiwan More articles by this author Hsin-Tzu Tsai Tainan, Taiwan More articles by this author Ai-Li Shiau Tainan, Taiwan More articles by this author Tzong-Shin Tzai Tainan, Taiwan More articles by this author Chao-Liang Wu Tainan, Taiwan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...