Advancing brain tumor precision care with nanomedicine

The prognosis of brain tumors is often poor. Enhancing brain tumor treatment is not only a critical clinical need but also a persistent scientific challenge. Radiotherapy plays a vital role in the current standard treatment regimen, with external radiotherapy being the traditional method. However, this approach faces significant hurdles due to its lack of specificity. Brain tumors tend to infiltrate healthy brain tissue, making complete surgical removal impossible. The residual tumor-initiating cells can develop into more aggressive recurrent tumors. Furthermore, brain tumors can release circulating tumor cells into the bloodstream, contributing to recurrence. Consequently, applying external radiotherapy locally to the head is inadequate, and whole-body radiation is not feasible. There is a pressing need for innovative radiotherapy techniques in clinical settings. Our goal is to create radiolabeled nanomedicine for brain tumor precision radiotherapy. Specifically, we aim to develop radioiodine-131-labeled gold nanoparticles (GNP) coated with nanobodies that target Poly(ADP-ribose) polymerase 1 (PARP1), referred to as [131I]GNP-PARP1, for targeted radiotherapy. Iodine-131 is a well-established therapeutic radionuclide, and PARP1 is a target located near DNA in tumor cells. This new radiotherapeutic agent is anticipated to selectively and effectively destroy tumor cells. We will assess [131I]GNP-PARP1 monotherapy and its combination therapy in mice with brain tumors, and investigate the mechanisms underlying the treatment response in different treatment settings. Additionally, we will employ our innovative PET agent alongside MRI to monitor treatment response. To date, no radiopharmaceuticals have been approved for clinical brain tumor radiotherapy. The outcomes of this project will offer a novel approach to brain tumor radiotherapy and provide significant insights into using nanomedicine to address this unmet clinical need.