Mineralized Lipid Nanoparticles Containing Gadolinium Enable Integrated X-ray Fluorescence Computed Tomography Imaging and Radiotherapy.

Abstract

Glioblastoma multiforme (GBM) poses a persistent clinical challenge due to its highly invasive nature, poor prognosis, and difficulty in achieving tumor-specific delivery across the blood-brain barrier (BBB). Here, we present a theranostic nanoplatform based on mineralized lipid vesicles encapsulating gadolinium ions (Gd³⁺) chelated by guanosine-5'-triphosphate (GTP), forming a dense and stable inorganic core. These Gd-mineralized vesicles demonstrate enhanced BBB penetration, prolonged tumor retention, and dual functionality for X-ray fluorescence computed tomography (XFCT) and cone-beam CT (CBCT) imaging-guided radiotherapy. This system enables high-resolution, high-contrast mapping of intratumoral Gd distribution, significantly enhancing radiotherapeutic efficacy through localized dose amplification. To our knowledge, this is the first application of GTP-mediated Gd mineralization in liposomes for dual-modality XFCT/CBCT-guided cancer therapy, offering a versatile and translational approach for precision imaging and radiosensitization in GBM.