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Small. 2013 Jun 24;9(12):2119-28. doi: 10.1002/smll.201202755. Epub 2013 Jan 20.

TGF-β1 conjugated to gold nanoparticles results in protein conformational changes and attenuates the biological function.

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  • 1Department of Urology, National Cheng Kung University Medical College, 1 University Road, Tainan 70101, Taiwan.

Abstract

Gold nanoparticles (AuNPs) are widely used as carriers or therapeutic agents due to their great biocompatibility and unique physical properties. Transforming growth factor-beta 1 (TGF-β1), a member of the cysteine-knot structural superfamily, plays a pivotal role in many diseases and is known as an immunosuppressive agent that attenuates immune response resulting in tumor growth. The results reported herein reflect strong interactions between TGF-β1 and the surface of AuNPs when incubated with serum-containing medium, and demonstrate a time- and dose-dependent pattern. Compared with other serum proteins that can also bind to the AuNP surface, AuNP-TGFβ1 conjugate is a thermodynamically favored compound. Epithelial cells undergo epithelial-mesenchymal transition (EMT) upon treatment with TGF-β1; however, treatment with AuNPs reverses this effect, as detected by cell morphology and expression levels of EMT markers. TGF-β1 is found to bind to AuNPs through S-Au bonds by X-ray photoelectron spectroscopy. Fourier transform infrared spectroscopy is employed to analyze the conformational changes of TGF-β1 on the surface of AuNPs. The results indicate that TGF-β1 undergoes significant conformational changes at both secondary and tertiary structural levels after conjugation to the AuNP surface, which results in the deactivation of TGF-β1 protein. An in vivo experiment also shows that addition of AuNPs attenuates 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 is 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. The findings demonstrate that AuNPs may be a promising agent for modulating tumor immunity through inhibiting immunosuppressive TGF-β1 signaling.

PMID:
23335450
DOI:
10.1002/smll.201202755
[PubMed - indexed for MEDLINE]
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