title: Guiding Brain-Tumor Surgery via Blood-Brain-Barrier-Permeable Gold Nanoprobes with Acid-Triggered MRI/SERRS Signals.
abstract: Surgical resection is a mainstay in the treatment of malignant brain tumors. Surgeons, however, face great challenges in distinguishing tumor margins due to their infiltrated nature. Here, a pair of gold nanoprobes that enter a brain tumor by crossing the blood-brain barrier is developed. The acidic tumor environment triggers their assembly with the concomitant activation of both magnetic resonance (MR) and surface-enhanced resonance Raman spectroscopy (SERRS) signals. While the bulky aggregates continuously trap into the tumor interstitium, the intact nanoprobes in normal brain tissue can be transported back into the blood stream in a timely manner. Experimental results show that physiological acidity triggers nanoparticle assembly by forming 3D spherical nanoclusters with remarkable MR and SERRS signal enhancements. The nanoprobes not only preoperatively define orthotopic glioblastoma xenografts by magnetic resonance imaging (MRI) with high sensitivity and durability in vivo, but also intraoperatively guide tumor excision with the assistance of a handheld Raman scanner. Microscopy studies verify the precisely demarcated tumor margin marked by the assembled nanoprobes. Taking advantage of the nanoprobes' rapid excretion rate and the extracellular acidification as a hallmark of solid tumors, these nanoprobes are promising in improving brain-tumor surgical outcome with high specificity, safety, and universality.
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Xihui
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yue
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Zining
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Mengjing
authors.initials: M
authors.lastname: Ke
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Sihan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Shanghai Cancer Center, Fudan University, 270 Dongan Road, Shanghai, 200032, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center of Analysis and Measurement, Fudan University, 220 Handan Road, Shanghai, 200433, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.|State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
mesh_terms: D001812:Blood-Brain Barrier; D001932:Brain Neoplasms; D005909:Glioblastoma; D006046:Gold; D006801:Humans; D008279:Magnetic Resonance Imaging; D049329:Nanostructures
chemical_list: D006046:Gold
keywords: brain tumors; gold nanoparticles; image-guided surgery; magnetic resonance imaging; surface-enhanced resonance Raman scattering