Injectable Biocompatible Zeolite Nanocrystals for Enhanced Tumor Oxygenation and MRI Imaging

Abstract

Tumor hypoxia significantly limits the effectiveness of radiotherapy, as oxygen is crucial for producing cancer-killing reactive oxygen species. To address this, we synthesized nanosized faujasite (PBS-Na-FAU) zeolite crystals using clinical-grade phosphate-buffered saline (PBS) as the solvent, ensuring preserved crystallinity, microporous volume, and colloidal stability. The zeolite nanocrystals showed enhanced safety profiles in vitro and ex vivo, and in vivo studies showed no apparent toxicity to animals. They demonstrated a high oxygen capacity with a release rate of 2.68 mg/L under hypoxic conditions. The introduction of gadolinium (Gd³⁺) into the zeolite nanocrystals by ion exchange, replacing three monovalent cations (Na⁺ and K⁺), led to an increased oxygen capacity of the sample. In situ Fourier transform infrared (FTIR) study revealed that Gd-containing zeolite (PBS-Gd-FAU) adsorbed ∼23% more oxygen at 20 kPa compared to the as-synthesized sample (PBS-Na-FAU). In vivo magnetic resonance imaging (MRI) demonstrated targeted oxygen delivery and release within brain tumors, revealing 14.91 and 17.10% differences in cerebral blood volume (CBV) between tumor and contralateral brain tissue after 15 and 20 min, respectively, compared to the control. T1 maps at 7 T indicated a relaxation rate of 9.254 mM^–1·s^–1 for PBS-Gd-FAU, twice that of commercial Gd-chelates. These findings highlight the potential of Gd-containing zeolite nanocrystals synthesized in PBS as a biocompatible platform for enhancing tumor oxygenation in anticancer therapy, with significant clinical translation potential.