Targeted Glioblastoma Treatment via Synthesis and Functionalization of Gold Nanoparticles With De Novo–Engineered Transferrin-Like Peptides: Protocol for a Novel Method

BACKGROUND: Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options due to the blood-brain barrier’s (BBB’s) 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. OBJECTIVE: 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. METHODS: The proposal involves multiple steps with rigorous quality control of AuNP synthesis, stabilization with surfactants, and polyethylene glycol coating. The engineered transferrin-like peptides will be synthesized and attached to the AuNPs’ surface, followed by the attachment of temozolomide and O6-methylguanine-DNA methyltransferase inhibitors. The resulting complex will undergo in vitro testing to assess BBB penetration, efficacy against GBM cells, and potential toxicity. RESULTS: 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 and surface plasmon resonance. Additionally, we will conduct pH stability tests to ensure our functionalized AuNPs retain their properties in acidic brain tumor microenvironments. CONCLUSIONS: 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 nanoparticle design optimization. This proposal anticipates inspiring future research and funding in neuro-oncology, presenting a potentially innovative and effective treatment option for GBM. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/49417