Outer Frame-Degradable Nanovehicles Featured with Near-Infrared Dual Luminescences for In Vivo Tracking of Protein Delivery in Cancer Therapy

In vivo monitoring of cargo protein delivery is critical for understanding the pharmacological efficacies and mechanisms during cancer therapy, but it still remains a formidable challenge because of the difficulty in observing non-fluorescent proteins at high resolution and sensitivity. Here we report an outer frame-degradable nanovehicle featured with near-infrared (NIR) dual luminescences for real-time tracking of protein delivery in vivo. Upconversion nanoparticles (UCNPs) and fluorophore-doped degradable macroporous silica (DS) with spectral overlap were coupled to form a core-shell nanostructure as a therapeutic protein nanocarrier, which was eventually enveloped with hyaluronic acid (HA) shell for preventing protein leakage and recognizing tumor sites. The DS layer served as both a container to accommodate the therapeutic proteins and a filter to attenuate upconversion luminescence (UCL) of the inner UCNPs. After the nanovehicles selectively accumulated at tumor sites and got into cancer cells, intr...