Abstract
Nanotechnology provides tremendous biomedical opportunities for cancer diagnosis, imaging, and therapy. In contrast to
conventional chemotherapeutic agents where their actual target delivery cannot be easily imaged, integrating imaging
and therapeutic properties into one platform facilitates the understanding of pharmacokinetic profiles, and enables
monitoring of the therapeutic process in each individual. Such a concept dubbed “theranostics” potentiates translational
research and improves precision medicine. One particular challenging application of theranostics involves imaging and
controlled delivery of nanoplatforms across blood-brain-barrier (BBB) into brain tissues. Typically, the BBB hinders
paracellular flux of drug molecules into brain parenchyma. BBB disrupting agents (e.g. mannitol, focused ultrasound),
however, suffer from poor spatial confinement. It has been a challenge to design a nanoplatform not only acts as a
contrast agent but also improves the BBB permeation. In this study, we demonstrated the feasibility of plasmonic gold
nanoparticles as both high-resolution optical contrast agent and focalized tumor BBB permeation-inducing agent. We
specifically examined the microscopic distribution of nanoparticles in tumor brain animal models. We observed that
most nanoparticles accumulated at the tumor periphery or perivascular spaces. Nanoparticles were present in both
endothelial cells and interstitial matrices. This study also demonstrated a novel photothermal-induced BBB permeation.
Fine-tuning the irradiating energy induced gentle disruption of the vascular integrity, causing short-term extravasation of
nanomaterials but without hemorrhage. We conclude that our gold nanoparticles are a powerful biocompatible contrast
agent capable of inducing focal BBB permeation, and therefore envision a strong potential of plasmonic gold
nanoparticle in future brain tumor imaging and therapy.
