Micro-CT Imaging of RGD-Conjugated Gold Nanorods Targeting Tumor<i>In Vivo</i>

Abstract

Gold nanomaterials as computed tomography (CT) contrast agents at lower X-ray dosage to get a higher contrast have advantages of longer imaging time and lower toxic side effects compared to current contrast agents. As a receptor for Cyclo (Arg-Gly-Asp-D-Phe-Lys) (RGD) peptide, integrin<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:msub><mml:mrow><mml:mi>α</mml:mi></mml:mrow><mml:mrow><mml:mi>v</mml:mi></mml:mrow></mml:msub><mml:msub><mml:mrow><mml:mi>β</mml:mi></mml:mrow><mml:mrow><mml:mn fontstyle="italic">3</mml:mn></mml:mrow></mml:msub></mml:math>is overexpressed on some tumor cells and tumor neovasculature. In this paper, we conjugated the RGD peptide on the surface of gold nanorods (AuNRs), designated as RGD-AuNRs, a promising candidate in applications such as tumor targeting and imaging capability for micro-CT imaging. Integrin<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:msub><mml:mrow><mml:mi>α</mml:mi></mml:mrow><mml:mrow><mml:mi>v</mml:mi></mml:mrow></mml:msub><mml:msub><mml:mrow><mml:mi>β</mml:mi></mml:mrow><mml:mrow><mml:mn fontstyle="italic">3</mml:mn></mml:mrow></mml:msub></mml:math>-positive U87 cells and integrin<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:msub><mml:mrow><mml:mi>α</mml:mi></mml:mrow><mml:mrow><mml:mi>v</mml:mi></mml:mrow></mml:msub><mml:msub><mml:mrow><mml:mi>β</mml:mi></mml:mrow><mml:mrow><mml:mn fontstyle="italic">3</mml:mn></mml:mrow></mml:msub></mml:math>-negative HT-29 cells were chosen to establish animal models relatedly and then texted the tumor targeting ability and imaging capability of RGD-AuNRs in vitro and in vivo . The MTT assay and stability measurement showed that RGD-conjugation eliminated their cytotoxicity and improved their biocompatibility and stability. Dark-field imaging of U87 cells and HT-29 cells testified the binding affinities and uptake abilities of RGD-AuNRs, and the results showed that RGD-AuNRs were more specifical to U87 cells. The enhanced micro-CT imaging contrast of intramuscular and subcutaneous injection illustrated the feasibility of RGD-AuNRs to be contrast agents. Furthermore, the micro-CT imaging of targeting U87 and HT-29 tumor models verified the targeting abilities of RGD-AuNRs.