Abstract
In this work, a peptide-modified, biodegradable, nontoxic, brain-tumor-targeting nanoprobe based on superparamagnetic iron oxide nanoparticles (SPIONs) (which have been commonly used as T2-weighted magnetic resonance (MR) contrast agents) was successfully synthesized and applied for accurate molecular MR imaging and sensitive optical imaging. PEPHC1, a short peptide which can specifically bind to epidermal growth factor receptor variant III (EGFRvIII) that is overexpressed in glioblastoma, was conjugated with SPIONs to construct the nanoprobe. Both in vitro and in vivo MR and optical imaging demonstrated that the as-constructed nanoprobe was effective and sensitive for tumor targeting with desirable biosafety. Given its desirable properties such as a 100 nm diameter (capable of penetration of the blood–brain barrier) and bimodal imaging capability, this novel and versatile multimodal nanoprobe could bring a new perspective for elucidating intracranial glioblastoma preoperative diagnosis and the accuracy of tumor resection.
Highlights
Tumor resection is one of the most promising clinical treatments of glioblastoma, which is commonly associated with high mortality and inevitable tumor recurrence
PEPHC1, a small peptide that can bind with the marker EGFRvIII that is overexpressed in glioblastoma, was grafted with the NHS group of DSPE-PEG-NHS through the amino group
As observed by transmission electron microscopy (TEM), the superparamagnetic iron oxide nanoparticles (SPIONs) suspended in hexane (Figure 1a) had a diameter of approximately 15 nm and the PNPs (Figure 1a) had a diameter of approximately 60 nm
Summary
Tumor resection is one of the most promising clinical treatments of glioblastoma, which is commonly associated with high mortality and inevitable tumor recurrence. To achieve a complete excision of tumors, the development of methods for accurate and efficient preoperative diagnosis and localization of glioblastoma is highly needed. Molecular imaging of tumor biomarkers is a powerful and important clinical diagnostic tool for noninvasive glioblastoma detection and characterization. Complete excision of the tumor relies on the accurate preoperative diagnosis and precise intraoperative localization of lesions during surgery. Given the lack of sensitivity in conventional MR imaging, the development of molecular MR imaging of tumor biomarkers is highly urgent for noninvasive, visual presentation of cancer aggressiveness and guidance of glioblastoma excision [5]. Gd-DTPA, as a commonly used positive contrast agent, despite its extensive application in T1-weighted MR imaging, has the disadvantages of unpredictable renal toxicity [6] and limited blood halftime [7]. The development of nanotechnology has made SPIONs promising candidates as molecular MR imaging probes as well [15,16,17,18]
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