Multiplex Three-Dimensional Mapping of Macromolecular Drug Distribution in the Tumor Microenvironment.

ABSTRACT: Macromolecular cancer drugs such as therapeutic antibodies and nanoparticles are well known to display slow extravasation and incomplete penetration into tumors, potentially protecting cancer cells from therapeutic effects. Conventional assays to track macromolecular drug delivery are poorly matched to the heterogeneous tumor microenvironment, but recent progress on optical tissue clearing and three-dimensional (3D) tumor imaging offers a path to quantitative assays with cellular resolution. Here, we apply transparent tissue tomography (T3) as a tool to track perfusion and delivery in the tumor and to evaluate target binding and vascular permeability. Using T3, we mapped anti-programmed cell death protein-ligand 1 (PD-L1) antibody distribution in whole mouse tumors. By measuring 3D penetra

SUBMITTER: Lee SS 

PROVIDER: S-EPMC6318001 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature