Chlorotoxin peptide-functionalized polyethylenimine-entrapped gold nanoparticles for glioma SPECT/CT imaging and radionuclide therapy

Lingzhou Zhao†,
Yujie Li†,
Jingyi Zhu†,
Na Sun,
Ningning Song,
Yan Xing,
He HuangEmail author and
Jinhua ZhaoEmail author

†Contributed equally

Journal of Nanobiotechnology201917:30

https://doi.org/10.1186/s12951-019-0462-6

Received: 10 November 2018
Accepted: 29 January 2019
Published: 19 February 2019

Abstract

Background

Malignant glioma is the most common and deadliest brain cancer due to the obstacle from indistinct tumor margins for surgical excision and blood brain barrier (BBB) for chemotherapy. Here, we designed and prepared multifunctional polyethylenimine-entrapped gold nanoparticles (Au PENPs) for targeted SPECT/CT imaging and radionuclide therapy of glioma.

Results

Polyethylenimine was selected as a template for sequential modification with polyethylene glycol (PEG), glioma-specific peptide (chlorotoxin, CTX) and 3-(4-hydroxyphenyl)propionic acid-OSu (HPAO), and were then used to entrap gold nanoparticles (Au NPs). After 131I radiolabeling via HPAO, the 131I-labeded CTX-functionalized Au PENPs as a multifunctional glioma-targeting nanoprobe were generated. Before 131I radiolabeling, the CTX-functionalized Au PENPs exhibited a uniform size distribution, favorable X-ray attenuation property, desired water solubility, and cytocompatibility in the given Au concentration range. The 131I-labeled CTX-functionalized Au PENPs showed high radiochemical purity and stability, and could be used as a nanoprobe for the targeted SPECT/CT imaging and radionuclide therapy of glioma cells in vitro and in vivo in a subcutaneous tumor model. Owing to the unique biological properties of CTX, the developed nanoprobe was able to cross the BBB and specifically target glioma cells in a rat intracranial glioma model.