Rapid Stereomicroscopic Imaging of HER2 Overexpression in Ex Vivo Breast Tissue Using Topically Applied Silica-Based Gold Nanoshells

摘要

Tumor margin detection for patients undergoing breast conservation surgery primarily occurs postoperatively. Previously, wedemonstrated that gold nanoshells rapidly enhance contrast of HER2 overexpression in ex vivo tissue sections. Our ultimateobjective, however, is to discern HER2 overexpressing tissue from normal tissue in whole, nonsectioned, specimens to facilitaterapid diagnoses. Here, we use targeted nanoshells to quickly and effectively visualize HER2 receptor expression in intact ex vivohuman breast tissue specimens. Punch biopsies of human breast tissue were analyzed after a brief 5-minute incubation with andwithout HER2-targeted silica-gold nanoshells using two-photon microscopy and stereomicroscopy. Labeling was subsequentlyverified using reflectance confocal microscopy, darkfield hyperspectral imaging, and immunohistochemistry to confirm levelsof HER2 expression. Our results suggest that anti-HER2 nanoshells used in tandem with a near-infrared reflectance confocalmicroscope and a standard stereomicroscope may potentially be used to discern HER2-overexpressing cancerous tissue fromnormal tissue in near real time and offer a rapid supplement to current diagnostic techniques.