Stealth Nanoparticleswith a “Self-Consuming”Shell for Long-Term Blood Vessel Imaging

The development of lanthanide-doped upconversion nanoparticle (UCNP)-based imaging with minimal autofluorescence and improved penetration depth is important in medical applications. Exogenous nanocarriers readily adsorb plasma proteins following intravenous administration (<0.5 min), resulting in the formation of a protein corona on the fixed surface. The protein corona facilitates UCNP interception by the immune system, preventing targeted delivery to disease sites. In this study, we report a novel surface-camouflaging strategy using lanthanide hydroxyl carbonate that is slowly dissolved by physiological phosphate in serum. The “self-consuming” inorganic-shell-modified UCNPs (denoted as UCSP-PEG) effectively reduce protein corona adhesion by more than 90% through a dissociation effect associated with the amphiphilic poly(ethylene glycol) (PEG)-modified UCNPs as determined in an ex vivo assay. The UCSP-PEG exhibits a prolonged blood circulation time (<i>t</i>_1/2 = 73.9 ± 9.5 min), 185 times that of camouflage materials without the “stealth” feature, and can employ upconverted luminescence (UCL) imaging to monitor tumor-related blood vessels for at least 120 min. Based on the superior optical properties of UCSP-PEG, the application of a UCL dual-channel stereoscope magnification imaging system has enabled the observation of capillaries with high resolution, offering a powerful tool for monitoring biological activities at the fine tissue level. This work provides a novel “stealth” nanovehicle, resisting blood protein adhesion based on a “self-consuming” effect that can significantly advance tissue imaging and target-specific cancer diagnosis.