Noninvasive Brain Tumor Imaging Using Red Emissive Carbonized Polymer Dots across the Blood-Brain Barrier

Abstract

Surgical resection is recognized as a mainstay in the therapy of malignant brain tumors. In clinical practice, however, surgeons face great challenges in identifying the tumor boundaries due to the infiltrating and heterogeneous nature of neoplastic tissues. Contrast-enhanced magnetic resonance imaging (MRI) is extensively used for defining the brain tumor in clinic. Disappointingly, the commercially available (MR) contrast agents show the transient circulation lifetime and poor blood-brain barrier (BBB) permeability, which seriously hamper their abilities in tumor visualization. In this work, red fluorescent carbonized polymer dots (CPDs) were systematically investigated with respect to their BBB-penetration ability. In summary, CPDs possess long excitation/emission wavelengths, low toxicity, high photostability, and excellent biocompatibility. CPDs exhibit high internalization in glioma cells in time- and dose-dependent procedures, and internalized CPDs locate mainly in endolysosomal structures. In vitro and in vivo studies confirmed the BBB permeability of CPDs, contributing to the early stage diagnosis of brain disorders and the noninvasive visualization of the brain tumor without compromised BBB. Furthermore, owing to the high tumor to normal tissue ratio of CPDs under ex vivo conditions, our nanoprobe holds the promise to guide brain-tumor resection by real-time fluorescence imaging during surgery.