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ACS Nano. 2019 Mar 26;13(3):2858-2869. doi: 10.1021/acsnano.8b04406. Epub 2019 Feb 4.

Nanomedicine for Spontaneous Brain Tumors: A Companion Clinical Trial.

Author information

1
Department of Radiology, Molecular Imaging Program at Stanford (MIPS) , Stanford University School of Medicine , Stanford , California 94305 , United States.
2
Department of Neurology and Neurological Sciences , Stanford University School of Medicine , Stanford , California 94304 , United States.
3
Department of Materials Science and Engineering , Stanford University , Stanford , California 94305 , United States.
4
Department of Surgical and Radiological Sciences , University of California at Davis , Davis , California 95616 , United States.
5
Department of Pathology, Microbiology and Immunology , University of California , Davis , California 95616 , United States.
6
Department of Bioengineering , Stanford University , Stanford , California 94305 , United States.
7
Stanford Neuroscience Institute , Stanford University School of Medicine , Stanford , California 94305 , United States.

Abstract

Nanoparticles' enhanced permeation and retention (EPR) variations due to tumor heterogeneity in naturally occurring brain tumors are commonly neglected in preclinical nanomedicine studies. Recent pathological studies have shown striking similarities between brain tumors in humans and dogs, indicating that canine brain tumors may be a valuable model to evaluate nanoparticles' EPR in this context. We recruited canine clinical cases with spontaneous brain tumors to investigate nanoparticles' EPR in different brain tumor pathologies using surface-enhanced Raman spectroscopy (SERS). We used gold nanoparticles due to their surface plasmon effect that enables their sensitive and microscopic resolution detection using the SERS technique. Raman microscopy of the resected tumors showed heterogeneous EPR of nanoparticles into oligodendrogliomas and meningiomas of different grades, without any detectable traces in necrotic parts of the tumors or normal brain. Raman observations were confirmed by scanning electron microscopy (SEM) and X-ray elemental analyses, which enabled localization of individual nanoparticles embedded in tumor tissues. Our results demonstrate nanoparticles' EPR and its variations in clinically relevant, spontaneous brain tumors. Such heterogeneities should be considered alongside routine preoperative imaging and histopathological analyses in order to accelerate clinical management of brain tumors using nanomedicine approaches.

KEYWORDS:

Raman; brain tumor; canine; clinical trial; glioma; gold; nanoparticle

PMID:
30714717
DOI:
10.1021/acsnano.8b04406

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