Tungsten disulfide-zeolitic imidazolate framework-8 nanoplatform loaded with gadolinium and conjugated with folic acid-PEG for bimodal CT/MRI imaging and 15 MV X-ray radiosensitization of glioblastoma and prostate cancer cells.

Glioblastoma multiforme and castration-resistant prostate cancer remain difficult to image and radiosensitize. We evaluated WS2@ZIF-8-Gd-FA-PEG, a folate-functionalized nanoplatform combining CT/MRI phantom contrast with 15 MV X-ray radiosensitization. The corrected conjugate was identified as FA-PEG-COOH, and surface functionalization was supported by 1H NMR, molecular-mass analysis, UV-visible spectroscopy, zeta potential, FTIR and XPS. In vitro BBB transport reached 8.46 ± 0.55% at 24 h for the targeted formulation versus 4.72 ± 0.31% for the non-targeted formulation, while barrier-integrity measurements remained stable. At 72 h, total Gd release was 9.4 ± 0.5%, 24.6 ± 1.2% and 61.5 ± 3.1% at pH 7.4, 6.5 and 5.0, respectively; free Gd3+ represented 1.8%, 5.9% and 18.7% of the initial Gd. CT attenuation was 24.6 HU per mg W mL-1 and MRI longitudinal relaxivity was 7.82 mM-1 s-1, compared with 4.01 mM-1 s-1 for gadodiamide. Targeted nanoparticles increased W uptake, and dose-response clonogenic analysis yielded SER10 values of 1.72, 1.61 and 1.18 for U87MG, PC-3 and MRC-5 cells, respectively. In a separate matched targeting-control experiment at 6 Gy, surviving fractions were 0.190 ± 0.018 in U87MG cells and 0.240 ± 0.019 in PC-3 cells. ROS scavenging and EPR/ESR spin trapping supported an association between oxidative stress, downstream cellular damage and loss of clonogenic survival. These data support receptor-associated uptake and in vitro radiosensitization while identifying pH-dependent Gd release as a safety consideration requiring in vivo evaluation.