Three-Dimensional Optical Mapping of Nanoparticle Distribution in Intact Tissues

The
role of tissue architecture in mediating nanoparticle transport, targeting,
and biological effects is unknown due to the lack of tools for imaging
nanomaterials in whole organs. Here, we developed a rapid optical
mapping technique to image nanomaterials in intact organs ex vivo and in three-dimensions (3D). We engineered a high-throughput
electrophoretic flow device to simultaneously transform up to 48 tissues
into optically transparent structures, allowing subcellular imaging
of nanomaterials more than 1 mm deep into tissues which is 25-fold
greater than current techniques. A key finding is that nanomaterials
can be retained in the processed tissue by chemical cross-linking
of surface adsorbed serum proteins to the tissue matrix, which enables
nanomaterials to be imaged with respect to cells, blood vessels, and
other structures. We developed a computational algorithm to analyze
and quantitatively map nanomaterial distribution. This method can
be universally applied to visualize the distribution and interactions
of materials in whole tissues and animals including such applications
as the imaging of nanomaterials, tissue engineered constructs, and
biosensors within their intact biological environment.