Cross-Link-Functionalized Nanoparticles for Rapid Excretion in Nanotheranostic Applications

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Molecular Imaging

Background:

• Near-infrared IIb (NIR-IIb) fluorophores often exhibit prolonged retention in vivo.
• Developing biocompatible probes with rapid clearance is crucial for advanced molecular imaging.

Purpose of the Study:

• To create novel NIR-IIb emitting quantum dots (QDs) with enhanced biocompatibility and rapid in vivo clearance.
• To functionalize these QDs for targeted imaging of CD8+ cytotoxic T lymphocytes (CTLs) in response to immunotherapy.
• To demonstrate the utility of these probes for multiplexed in vivo imaging.

Main Methods:

• Functionalization of core/shell lead sulfide/cadmium sulfide quantum dots (PbS/CdS QDs) with a novel cross-linked amphiphilic polymeric coating (P3 coating).
• Conjugation of P3-QDs to an engineered anti-CD8 diabody (Cys-diabody) for specific targeting of CTLs.
• Two-plex molecular imaging using P3-QDs and down-conversion Erbium nanoparticles (ErNPs) with NIR-IIb light sheet microscopy.

Main Results:

• The P3 coating ensured high biocompatibility and >90% excretion of QDs within 2 weeks post-administration.
• Achieved real-time, in vivo, cellular-resolution imaging of PD-L1 positive tumor cells and CTLs.
• Demonstrated imaging of tumor angiogenesis and deep lymph nodes with a high signal-to-background ratio (up to ~170).

Conclusions:

• The novel P3-coated QDs offer a promising solution for rapid clearance and biocompatibility in NIR-IIb imaging.
• This platform enables effective in vivo monitoring of therapeutic responses, particularly for immunotherapy targeting CTLs.
• The developed imaging approach facilitates detailed visualization of the tumor microenvironment and immune cell infiltration.