胶质母细胞瘤（GBM）是一种侵袭性的脑肿瘤，由于血脑屏障的阻碍和化疗的内在耐药性，目前治疗选择有限。功能化转铁蛋白肽的金纳米颗粒（AuNPs）显示出在克服这些挑战方面的潜力，增强药物输送到大脑，并减轻化疗耐药性。本研究的主要目标是建立一个详细的协议，用于合成和稳定AuNPs，将其功能化为新颖的转铁蛋白肽，并与化疗药物替莫唑胺结合。此策略旨在改善血脑屏障上药物输送，并绕过化疗耐药性。第二目标包括评估合成纳米复合物的安全性和潜在体内使用性。 该提案涉及多个步骤，严格控制AuNP合成质量，使用表面活性剂稳定它们，并进行聚乙二醇（PEG）包覆。将合成转铁蛋白肽并附着到AuNPs表面，然后进行替莫唑胺和MGMT抑制剂的结合。结果复合物将进行体外测试，以评估其穿越血脑屏障能力、对GBM细胞的疗效和潜在毒性。 初步实验和模拟结果表明已成功合成和稳定了AuNPs，并成功将转铁蛋白肽附着。我们建议使用傅里叶变换红外光谱（FTIR）和表面等离子共振（SPR）进行肽附着验证。此外，我们将进行pH稳定性测试，以确保我们功能化的AuNPs在酸性脑肿瘤微环境中保持其特性。 用新颖的转铁蛋白肽功能化AuNPs代表了一种治疗GBM的新方法。我们的策略为药物通过血脑屏障输送和减轻化疗耐药性打开了新的途径。尽管我们目前主要关注体外研究和计算模拟，但成功完成将会带来进一步的发展，包括体内研究和纳米颗粒设计的优化。该提案预计在神经肿瘤学领域激发未来的研究和资金，提供一种潜在的创新和有效的GBM治疗选择。

Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options due to the blood-brain barrier's (BBB) impedance and inherent resistance to chemotherapy. Gold nanoparticles (AuNPs) functionalized with transferrin-like peptides show promise in overcoming these challenges, enhancing drug delivery to the brain, and reducing chemotherapy resistance.The primary goal of this study is to establish a detailed protocol for synthesizing and stabilizing AuNPs, functionalizing them with de novo-engineered transferrin-like peptides, and conjugating them with the chemotherapeutic agent temozolomide. This strategy aims to improve drug delivery across the BBB and circumvent chemotherapy resistance. The secondary objective includes an assessment of the safety and potential for in vivo use of the synthesized nanoparticle complex.The proposal involves multiple steps with rigorous quality control of AuNP synthesis, stabilization with surfactants, and polyethylene glycol (PEG) coating. The engineered transferrin-like peptides will be synthesized and attached to the AuNPs surface, followed by the attachment of temozolomide and MGMT inhibitors. The resulting complex will undergo in vitro testing to assess BBB penetration, efficacy against GBM cells, and potential toxicity.Initial preliminary experiments and simulations suggest successful synthesis and stabilization of AuNPs and effective attachment of transferrin-like peptides. We propose peptide attachment verification using Fourier Transform Infrared Spectroscopy (FTIR) and Surface Plasmon Resonance (SPR). Additionally, we will conduct pH stability tests to ensure our functionalized AuNPs retain their properties in acidic brain tumor microenvironments.The proposed functionalization of AuNPs with de novo-engineered transferrin-like peptides represents a novel approach to GBM treatment. Our strategy opens new avenues for drug delivery across the BBB and chemotherapy resistance reduction. While we primarily focus on in-vitro studies and computational modeling at this stage, successful completion will lead to further development, including in-vivo studies and NP design optimization. This proposal anticipates inspiring future research and funding in neuro-oncology, presenting a potentially innovative and effective treatment option for GBM.