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Item Gold nanoparticles conjugated with epidermal growth factor and gadolinium for precision delivery of contrast agents in magnetic resonance imaging(Springer-Verlag London Ltd.) Queiroz, Marinho de; Veriato, Thaís da Silva; Raniero, Leandro José; Castilho, Maiara LimaThe utilization of contrast agents in magnetic resonance imaging (MRI) has become increasingly important in clinical diagnosis. However, the low diagnostic specificity of this technique is a limiting factor for the early detection of tumors. To develop a new contrast agent with a specific target for early stage tumors, we present the synthesis and characterization of a nanocontrast composed of gold nanoparticles (AuNPs), gadopentetic acid (Gd-DTPA), and epidermal growth factor (EGF). Carbodiimide-based chemistry was utilized to modify Gd-DTPA for functionalization with AuNPs. This resulted in the formation of the Au@Gd-EGF nanocontrast. The relaxation rate (1/T1) of the nanocontrast was analyzed using MRI, and cytotoxicity was determined based on cell viability and mitochondrial activity in a human breast adenocarcinoma cell line. Fourier-transform infrared spectroscopy analysis confirmed the effectiveness of carbodiimide in the formation of the Gd-DTPA-cysteamine complex in the presence of bands at 930, 1042, 1232, 1588, and 1716 cm-1. The complexes exhibited good interactions with the AuNPs. However, the signal intensity of the Au@Gd-EGF nanocontrast was lower than that of the commercial contrast agent because the r1/r2 relaxivities of the Gd-DTPA-based contrast agents were lower than those of the gadoversetamide-based molecules. The Au@Gd-EGF nanocontrast agent exhibited good biocompatibility, low cytotoxicity, and high signal intensity in MRI with active targeted delivery, suggesting significant potential for future applications in the early diagnosis of tumors.Item Chlorin e6-EGF conjugated gold nanoparticles as a nanomedicine based therapeutic agent for triple negative breast cancer(Elsevier) Castilho, Maiara Lima; Jesus, Viviane Paula dos Santos; Vieira, Paula Fonseca Antunes; Hewitt, Kevin Cecil; Raniero, Leandro JoséTo develop a treatment modality for triple-negative breast cancer, we investigated the efficacy of a bifunctional theranostic nanoprobes (BN) during Photodynamic Therapy (PDT) on human breast carcinoma and normal human cells. The BN is a 21 nm gold nanoparticles functionalized with Chlorin e6 (Ce6) and Epidermal Growth Factor (EGF). Attachment to gold nanoparticle stabilizes Ce6 while EGF acts as a cancer cell targeting agent. Fluorescence Spectroscopy and Confocal Fluorescence Microscopy revealed a gradual uptake of nanoprobes into cancer cells at an average rate of 63 BN/min. Cell viability assays showed that 0.2 μg/mL BN concentration was highly cytotoxic to cancer cells (86 %), but not normal cells. At this concentration, 58 % cancer cells were necrotic and 38 % apoptotic, while the reactive oxygen species (ROS) was 9-fold higher in cancer cells compared to normal. Overall, results suggest that BN mediated PDT can achieve targeted cancer cell death with high efficiency.