Large-Scale 3D Optical Mapping and Quantitative Analysisof Nanoparticle Distribution in Tumor Vascular Microenvironment
2020
Nanoparticles
(NPs) are a promising carrier for cancer therapeutics.
Systemically administered NPs are transported to tumor tissues via
the bloodstream, extravasated from microvessels, and delivered to
cancer cells. The distribution of NPs in the tumor vascular microenvironment
critically determines the therapeutic efficacy of NP-delivered drugs,
but its precise assessment in 3D across a large volume remains challenging.
Here, an analytical platformtermed OMNIA (for Optical Mapping
of Nanoparticles and Image Analysis)integrating tissue clearing,
high-resolution optical imaging, and semiautomated image analysis
is presented, which enables accurate, unbiased, and quantitative analysis
of the distribution of NPs in relation to the vasculature across a
large 3D volume. Application of OMNIA to tumor tissues revealed higher
accumulation and more efficient extravasation of NPs in the tumor
periphery than the core. Time-course analysis demonstrated that the
accumulation of NPs in tumor peaked at 24 h after injection, but the
relative distribution of NPs from the vasculature remained remarkably
stable over time. Comparisons between 45- and 200-nm-sized NPs showed
a lower accumulation of smaller NPs in tumors relative to the liver,
yet better vessel permeation. Together, our results demonstrate that
OMNIA facilitates precise and reliable evaluation of NP biodistribution,
and mechanistic investigations on NP delivery to tumor tissues.
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