Small-sized gadolinium oxide based nanoparticles for high-efficiency theranostics of orthotopic glioblastoma

Glioblastoma (GBM) is one of the most malignant tumors with poor prognosis and outcomes. Although smaller particle size can lead to higher blood-brain barrier (BBB)-permeability of the nanomaterials, most of the reported BBB-crossable nanomaterials for targeted GBM therapy are larger than 24 nm. To...

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Published in:Biomaterials 2020-03, Vol.235, p.119783-119783, Article 119783
Main Authors: Shen, Zheyu, Liu, Ting, Yang, Zhen, Zhou, Zijian, Tang, Wei, Fan, Wenpei, Liu, Yijing, Mu, Jing, Li, Ling, Bregadze, Vladimir I., Mandal, Swadhin K., Druzina, Anna A., Wei, Zhenni, Qiu, Xiaozhong, Wu, Aiguo, Chen, Xiaoyuan
Format: Article
Language:English
Subjects:
Animals
Blood-brain barrier
Gadolinium
Glioblastoma - diagnostic imaging
Glioblastoma - therapy
High contrast magnetic resonance imaging
Magnetic Resonance Imaging
Mice
Nanoparticles
Orthotopic glioblastoma
Precision Medicine
Radiosensitization
Small-sized gadolinium oxide based nanoparticles
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Summary:Glioblastoma (GBM) is one of the most malignant tumors with poor prognosis and outcomes. Although smaller particle size can lead to higher blood-brain barrier (BBB)-permeability of the nanomaterials, most of the reported BBB-crossable nanomaterials for targeted GBM therapy are larger than 24 nm. To realize theranostics of GBM, co-loading of therapeutic and diagnostic agents on the same nanomaterials further results in larger particle size. In this study, we developed a kind of novel BBB-transportable nanomaterials smaller than 14 nm for high-efficiency theranostics of GBM (i.e., high contrast magnetic resonance imaging (MRI) and radiosensitization of GBM). Typically, poly(acrylic acid) (PAA) stabilized extremely small gadolinium oxide nanoparticles with modification of reductive bovine serum albumin (ES-GON-rBSA) was synthesized in water phase, resulting in excellent water-dispersibility. RGD dimer (RGD2, Glu-{Cyclo[Arg-Gly-Asp-(D-Phe)-Lys]}2) and lactoferrin (LF) were then conjugated to the ES-GON-rBSA to obtain composite nanoparticle ES-GON-rBSA-LF-RGD2 with extraordinary relaxivities (r1 = 60.8 mM−1 s−1, r2/r1 = 1.1). The maximum signal enhancement (ΔSNR) for T1-weighted MRI of tumors reached up to 423 ± 42% at 12 h post-injection of ES-GON-rBSA-LF-RGD2, which is much higher than commercial Gd-chelates (
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2020.119783