Cross‐Link‐Functionalized Nanoparticles for Rapid Excretion in Nanotheranostic Applications
- 18 July 2020
- journal article
- research article
- Published by Wiley in Angewandte Chemie
- Vol. 59 (46), 20552-20560
- https://doi.org/10.1002/anie.202008083
Abstract
Nanoparticles have been widely investigated for preclinical animal models as imaging, therapeutic or theranostic agent. However, a very limited number of nanoscale materials are approved for human use due to retention and toxicity concerns. Recent years have seen in vivo fluorescence imaging in the long end of the second near infrared window (NIR‐IIb, 1,500‐1,700 nm), affording deeper tissue penetration and higher imaging clarity owing to reduced light scattering and near‐zero autofluorescence. Most NIR‐IIb fluorophores are nanoparticle based probes with long retention in the body. Here, we applied a novel cross‐linked coating to functionalize core/shell lead sulfide/cadmium sulfide quantum dots (PbS/CdS QDs) emitting at ~1,600 nm. The coating was comprised of an amphiphilic polymer followed by three crosslinked amphiphilic polymeric layers (branched PEG‐linear PAA‐branched PEG, P 3 coating), imparting high biocompatibility and > 90% excretion of QDs within 2 weeks of intravenous administration. The P 3 ‐QDs were utilized for conjugation to an engineered anti‐CD8 diabody to afford in vivo molecular imaging of CD8+ cytotoxic T lymphocytes (CTLs) in response to anti‐PD‐L1 therapy. Two‐plex molecular imaging in combination with down‐conversion Er nanoparticles was performed for real‐time in vivo monitoring of PD‐L1+ tumor cells and CD8+ CTLs with cellular resolution by non‐invasive NIR‐IIb light sheet microscopy (LSM). In another application, angiogenesis in the tumor microenvironment was imaged with P 3 ‐QDs conjugated to TRC105, a chimeric monoclonal antibody against CD105. Further, P 3 ‐QDs afforded imaging of lymph nodes deep in the body with a signal‐to‐background ratio of up to ~170. Lastly, we show that the P 3 coating on magnetic nanoparticles also afforded rapid excretion in < 2 weeks, establishing generality of the approach. The ability of eliminating various nanoparticles from a body opens up many possibilities of nanomedicine for human use.Funding Information
- National Institutes of Health (DP1-NS-105737)
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