Stealth Nanoparticles with a "Self-Consuming" Shell for Long-Term Blood Vessel Imaging

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Medical Imaging

Background:

• Upconversion nanoparticle (UCNP)-based imaging offers advantages like minimal autofluorescence and deep tissue penetration for medical applications.
• Protein corona formation on nanocarriers after intravenous administration hinders targeted delivery by triggering immune responses.
• Effective strategies are needed to prevent protein adsorption and improve the in vivo performance of UCNPs.

Purpose of the Study:

• To develop a novel surface-camouflaging strategy for UCNPs to reduce protein corona formation and enhance their stealth properties.
• To evaluate the efficacy of the camouflaged UCNPs in reducing protein adhesion and prolonging blood circulation time.
• To demonstrate the utility of these UCNPs for in vivo imaging of tumor vasculature and fine tissue structures.

Main Methods:

• A "self-consuming" inorganic-shell modification using lanthanide hydroxyl carbonate was applied to UCNPs, creating amphiphilic poly(ethylene glycol) (PEG)-modified UCNPs (UCSP-PEG).
• Protein corona adhesion was quantified using ex vivo assays to compare UCSP-PEG with unmodified UCNPs.
• Blood circulation time and in vivo upconverted luminescence (UCL) imaging of tumor-related blood vessels were assessed in animal models.

Main Results:

• The UCSP-PEG demonstrated a reduction in protein corona adhesion by over 90% compared to controls.
• UCSP-PEG exhibited a significantly prolonged blood circulation half-life (73.9 ± 9.5 min), 185 times longer than UCNPs without the stealth feature.
• UCL imaging successfully monitored tumor-related blood vessels for over 120 minutes, with high-resolution capillary observation possible using a dual-channel stereoscope magnification system.

Conclusions:

• The novel "self-consuming" inorganic shell effectively camouflages UCNPs, minimizing protein adhesion and immune system interception.
• The enhanced stealth properties and prolonged circulation time of UCSP-PEG make them promising nanovehicles for advanced tissue imaging.
• This technology holds potential for improving targeted cancer diagnosis and monitoring biological activities at the fine tissue level.