Guiding Brain-Tumor Surgery via Blood-Brain-Barrier-Permeable Gold Nanoprobes with Acid-Triggered MRI/SERRS Signals

Xihui Gao, Qi Yue, Zining Liu, Mengjing Ke, Xingyu Zhou, Sihan Li, Jianping Zhang, Ren Zhang, Liang Chen, Ying Mao, Cong Li

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalAdvanced Materials
DOIs
StateAccepted/In press - 2017

Keywords

  • Brain tumors
  • Gold nanoparticles
  • Image-guided surgery
  • Magnetic resonance imaging
  • Surface-enhanced resonance Raman scattering

ASJC Scopus subject areas

  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering

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