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.

Integration of gadolinium in nanostructure for contrast enhanced‐magnetic resonance imaging

“…Likewise, plasmonic nanoparticles have also been attracted tremendous attention in biomedical research and applications because of their versatile synthetic methodology, unique physiochemical properties, and good biocompatibility (Bhattarai et al, ; Heffern et al, ; Nicolay et al, ; Zhang et al, ). The unique localized surface plasmon resonance properties of plasmonic NPs such as gold (Au) and silver (Ag)‐based nanomaterials with a variety of shapes (spherical, rod, star) and sizes have been used in bio‐imaging, cancer targeting, and cancer therapy (Gao et al, ; Marasini et al, ; Pitchaimani et al, ). Significant efforts have been applied to engineer multifunctional theranostic nanoconstruct by conjugating small molecule GBCA and therapeutic cargo for image‐guided therapy (Lohrke et al, ; Meola, Rao, Chaudhary, Sharma, & Chang, ).…”

“…(Reprinted with permission from Pitchaimani et al (2017). Copyright 2017 American Scientific Publishers) star) and sizes have been used in bio-imaging, cancer targeting, and cancer therapy (Gao et al, 2017;Marasini et al, 2018;Pitchaimani et al, 2017). Significant efforts have been applied to engineer multifunctional theranostic nanoconstruct by conjugating small molecule GBCA and therapeutic cargo for image-guided therapy (Lohrke et al, 2016;Meola, Rao, Chaudhary, Sharma, & Chang, 2018).…”

“…The intensities of the characteristic Raman twin peak were quantified in a 5 × 5 grid covering the tumor cutting bed. (Reprinted with permission from Gao et al (2017). Copyright 2017 John Wiley and Sons) when compared to that of Gd-DTPA at pH 5.5 in a 7.0 T micro-MRI scanner.…”

Enhanced blood-brain-barrier penetrability and tumor-targeting efficiency by peptide-functionalized poly(amidoamine) dendrimer for the therapy of gliomas

“…This strategy has attracted much attention, yet the efficacy of drugs and the pharmacokinetics remain to be confirmed. With the development of nanotechnology and nanomedicine in the recent decades, various drug delivery vehicles, such as liposomes [21][22][23], hydrogels [24], micelles [25,26], polymers [27][28][29] and inorganic nanoparticles [30][31][32][33][34][35] have been developed to incorporate therapeutics and to deliver them into tumor sites and CNS.…”

Glioblastoma cells labeled by robust Raman tags for enhancing imaging contrast

“…Therefore, various imaging methods other than fluorescence imaging have recently been applied to brain tumor surgery such as OCT (optical coherence tomography), Raman imaging, intraoperative MRI, intraoperative ultrasound etc [13][14][15][16][17][18][19][20][21]. Among them, Raman imaging provides good spatial resolution and spectral features distinguishable from background autofluorescence.…”