Accepted for/Published in: JMIR Research Protocols
Date Submitted: May 28, 2023
Open Peer Review Period: May 28, 2023 - Jul 23, 2023
Date Accepted: Jul 24, 2023
Date Submitted to PubMed: Aug 2, 2023
(closed for review but you can still tweet)
Targeted Glioblastoma Treatment via Synthesis and Functionalization of Gold Nanoparticles with De Novo-Engineered Transferrin-like Peptides: A Novel Method Protocol
ABSTRACT
Background:
Glioblastoma multiforme (GBM) is a particularly aggressive brain tumor with limited treatment options due to the blood-brain barrier (BBB) and resistance to chemotherapy. Gold nanoparticles (AuNPs) capable of interacting with transferrin receptors (TfR) through attached peptides individually have shown promise in enhancing drug delivery to the brain.
Objective:
The primary objective is to propose a novel method for enhancing GBM treatment by a protocoled synthesis and stabilization of AuNPs, then functionalizing them with de novo-engineered transferrin-like peptides and the chemotherapeutic agent temozolomide. The aim is to enhance drug delivery across the BBB and overcome chemotherapy resistance. The secondary objective is to evaluate the safety of the conjugated compound and assess its potential for in vivo use.
Methods:
The proposal involves several stages. First, AuNPs will be synthesized based on our protocol and stabilized with surfactants, then coated with polyethylene glycol (PEG). Next, transferrin-like peptides will be synthesized and attached to the AuNPs’ surface. Temozolomide and MGMT inhibitors will also be attached to or encapsulated within the AuNPs. The resulting compound will be tested for its ability to cross the BBB and its efficacy against GBM cells in vitro. The compound's potential toxicity will also be evaluated.
Results:
Initial experiments suggest that our protocol for the synthesis and stabilization of AuNPs can be reproduced for biomedical applications. Simulations indicate that the proposed transferrin-like peptides can be effectively attached to the AuNPs. Further results have not been obtained at this time.
Conclusions:
The functionalization of AuNPs with de novo-engineered transferrin-like peptides presents an innovative approach for the treatment of GBM. Future prospects include enhancing the treatment in neuro-oncology that are currently difficult to treat due to the BBB. As funding is not anticipated at this time, it is hoped that this proposal will inspire further research in this field.
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