Two-Order Targeted Brain Tumor Imaging by Using an Optical/Paramagnetic Nanoprobe across the Blood Brain Barrier
Citations Over TimeTop 10% of 2011 papers
Abstract
Surgical resection is a mainstay of brain tumor treatments. However, the completed excision of malignant brain tumor is challenged by its infiltrative nature. Contrast enhanced magnetic resonance imaging is widely used for defining brain tumor in clinic. However its ability in tumor visualization is hindered by the transient circulation lifetime, nontargeting specificity, and poor blood brain barrier (BBB) permeability of the commercially available MR contrast agents. In this work, we developed a two-order targeted nanoprobe in which MR/optical imaging reporters, tumor vasculature targeted cyclic [RGDyK] peptides, and BBB-permeable Angiopep-2 peptides are labeled on the PAMAM-G5 dendrimer. This nanoprobe is supposed to first target the α(V)β(3) integrin on tumor vasculatures. Increased local concentration of nanoprobe facilitates the association between BBB-permeable peptides and the low-density lipoprotein receptor-related protein (LRP) receptors on the vascular endothelial cells, which further accelerates BBB transverse of the nanoprobe via LRP receptor-mediated endocytosis. The nanoprobes that have penetrated the BBB secondly target the brain tumor because both α(V)β(3) integrin and LRP receptor are highly expressed on the tumor cells. In vivo imaging studies demonstrated that this nanoprobe not only efficiently crossed intact BBB in normal mice, but also precisely delineated the boundary of the orthotropic U87MG human glioblastoma xenograft with high target to background signal ratio. Overall, this two-order targeted nanoprobe holds the promise to noninvasively visualize brain tumors with uncompromised BBB and provides the possibility for real-time optical-image-guided brain tumor resection during surgery.
Related Papers
- → Quantitative Assessment of Copper(II) in Wilson’s Disease Based on Photoacoustic Imaging and Ratiometric Surface-Enhanced Raman Scattering(2021)92 cited
- → A ratiometric fluorescent nanoprobe for H2O2sensing and in vivo detection of drug-induced oxidative damage to the digestive system(2014)47 cited
- → A new type of silica-coated Gd2(CO3)3:Tb nanoparticle as a bifunctional agent for magnetic resonance imaging and fluorescent imaging(2012)39 cited
- → A biocompatible ratiometric fluorescent nanoprobe for intracellular hydrogen sulfide accurate detection based on rare earth nanoparticle(2022)4 cited
- → Cation Exchange Strategy to Construct a Targeting Nanoprobe for Enhanced Positive MR Imaging Capability(2020)