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Gold Nanoparticles Synthesized with Triple-Negative Breast Cancer Cell Lysate Enhance Antitumoral Immunity: A Novel Synthesis Method
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DOI：10.3390/ph18030330.png)
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Abstract
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Background: Gold nanoparticles enhance immunity, promotes antigen uptake by antigen-presenting cells (APCs), and boost the response against tumor antigens; therefore, they are a promising delivery vehicle. Tumor lysates have shown favorable responses as inductors of anti-cancer immunity, but the effectiveness of these treatments could be improved. Hybrid nanosystems gold nanoparticles with biomolecules have been show promising alternative on uptake, activation and response on immune system. Objectives: This study's objective was to develop a method of synthesizing gold nanoparticles employing a triple-negative breast cancer (4T1) cell lysate (AuLtNps) as a reducing agent to increase immunogenicity against breast cancer cells. Methods: Nanoparticle formation, size, and zeta potential were confirmed by surface plasmon resonance, dynamic light scattering, and transmission electron microscopy. Protein concentration was quantified using a Pierce BCA assay. The cytotoxic effects of treatments on murine macrophages were assessed, along with nanoparticle and tumor lysate uptake via epifluorescence microscopy. Using a murine model, cytokine secretion profiles were determined, and the efficacy in inhibiting the implantation of a 4T1 model was evaluated. Results/Conclusions: AuLtNps exhibited higher protein content than tumor lysate alone, leading to increased uptake and phagocytosis in murine macrophages, as confirmed by epifluorescence microscopy. Cytokine secretion analysis showed a proinflammatory response, with increased CD8+ and CD22+ lymphocytes and upregulation of APC markers (CD14, CD80, CD86, and MHC II+). Splenocytes demonstrated specific lysis of up to 40% against 4T1 tumor cells. In a murine model, AuLtNPs effectively inhibited tumor implantation, achieving an improved 90-days survival rate, highlighting their potential as an immunotherapy for triple-negative breast cancer.
Keywords:
antigen presentation
breast cancer immunotherapy
gold nanoparticles
immune system activation
tumor cell lysates
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