Virus-inspired hollow mesoporous gadolinium-bismuth nanotheranostics for magnetic resonance imaging-guided synergistic photodynamic-radiotherapy.

The anti-tumor efficacy of single photodynamic therapy (PDT) and radiotherapy (RT) has been greatly affected by inadequate tumor uptake of photo/radiation sensitizers, limited laser penetration depth, and radiation sickness caused by high doses of X-rays. Here, we report a biomimetic coronavirus-inspired hollow mesoporous gadolinium/bismuth nanocarrier loaded with a new NIR photosensitizer HB (referred to as HB@VHMBi-Gd) for magnetic resonance imaging (MRI)-guided synergistic photodynamic-RT. HB@VHMBi-Gd displayed a faster cellular uptake rate than the conventional spherical HMBi-Gd loaded with HB (HB@SHMBi-Gd) because of the rough surface-enhanced adhesion. After intravenous injection, HB@VHMBi-Gd was efficiently delivered to the tumor and rapidly invaded the tumor cells by surface spikes. Interestingly, lysosomal acidity could trigger the degradation of VHMBi-Gd to produce ultrasmall nanoparticles to amplify the X-ray attenuation ability and enhance MRI contrast and radiosensitization. Under laser and X-ray irradiation, HB@VHMBi-Gd significantly enhanced 1 O2 generation from HB to induce activation of caspase 9/3 and inhibition of C-myc, while enhancing hydroxyl radical generation from Bi2 O3 to induce intense DNA breakage. By synergistically inducing cell apoptosis by distinct reactive oxygen species (ROS), HB@VHMBi-Gd exhibited superior anticancer efficacy with ∼90% tumor inhibition. We envision that biomimetic virus-inspired hollow hybrid metal nanoparticles could provide a promising strategy for imaging-guided synergistic photodynamic-RT. This article is protected by copyright. All rights reserved.