Protein nanocages (PNCs) have been recognized as a promising platform for nanomedicine innovation. Real-time in vivo tracking of PNCs can provide critically important information for the development of PNC-based diagnostics and therapeutics.

On the basis of previous study and by cooperating with the team led by Prof. Qiangbin Wang in Suzhou Institute of Nano-Tech and Nano-Bionics, CAS, the research group led by Prof. Feng Li in WIV, demonstrated a general strategy for monitoring the behaviors of PNCs in vivo by encapsulating a Ag2S quantum dot (QD) with fluorescence in the second near-infrared window (NIR-II, 1000–1700 nm) inside the PNC, using simian virus 40 (SV40) PNC (PNCSV40) as a model. Benefiting from the high spatiotemporal resolution and deep tissue penetration of NIR-II fluorescence imaging, the dynamic distribution of the PNCSV40 in living mice was tracked in real time with high fidelity, and adopting the PEGylation strategy, surface chemistry-dependent in vivo behaviors of PNCSV40 were clearly revealed.  

This study represents the first evidence of real-time tracking of the intrinsic behaviors of PNCs in vivo without interference in PNC-host interactions by encapsulating nanoprobes inside. The as-described imaging strategy will facilitate the study of interactions between exogenously introduced PNCs and host body and prompt the development of future protein-based drugs, sensors, and high-efficacy targeted delivery systems.