Magnetic and near-infrared-II fluorescence Au–Gd nanoclusters for imaging-guided sensitization of tumor radiotherapy

The significant role of multifunctional nanoprobes with complementary advantages in magnetic and near-infrared-II (NIR-II, 1000-1700 nm) fluorescence properties has been documented in precision cancer theranostics. However, certain limitations, including the large size (>10 nm), low NIR-II fluorescence quantum yield (QY < 1.0%), and inefficient magnetic performance (relaxation rate < 5.0 s-1 mM-1) of nanoprobes, restrict their biomedical applications and clinical translation. Albumin-based biomineralization was adopted to prepare bright NIR-II Au NCs, which were further conjugated with DTPA and Gd ions to produce magnetic and NIR-II Au-Gd NCs. Albumin-based biomineralization helped to develop ultrasmall Au-Gd nanoclusters with ultrasmall size (∼2 nm), high NIR-II fluorescence QY (∼3.0%), and effective magnetic resonance imaging (MRI) performance (relaxation rate (r1) = 22.6 s-1 mM-1). On the one hand, Au-Gd NCs achieved NIR-II fluorescence and MRI dual-modal imaging of tumors with a high signal-to-background ratio (SBR = 8.2) in mice. On the other hand, their effective metabolism simultaneously through the kidney and liver minimized their toxicity in vivo. Moreover, compared to the control group, the survival time of tumor-bearing mice was extended by three times when Au-Gd NCs with high-Z elements were used to perform dual-modal imaging-guided sensitization of tumor radiotherapy. Thus, ultrasmall nanoprobes with complementary imaging modalities and therapeutic functions manifest great potential in cancer precision diagnosis and therapy.