Oncotarget

Research Papers:

Asn-Gly-Arg-modified polydopamine-coated nanoparticles for dual-targeting therapy of brain glioma in rats

Jiangang Hu, Xiang Zhang, Zuhuang Wen, Ying Tan, Ning Huang, Si Cheng, Huzhi Zheng _ and Yuan Cheng

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Oncotarget. 2016; 7:73681-73696. https://doi.org/10.18632/oncotarget.12047

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Abstract

Jiangang Hu1,2, Xiang Zhang1,2, Zuhuang Wen3, Ying Tan1, Ning Huang1, Si Cheng4, Huzhi Zheng3, Yuan Cheng1

1Department of Neurosurgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

2Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging of Chongqing Medical University, Chongqing, 400016, China

3College of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China

4Department of Orthopaedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

Correspondence to:

Huzhi Zheng, email: [email protected]

Yuan Cheng, email: [email protected]

Keywords: Asn-Gly-Arg, polydopamine, dual-targeting, gliomas

Received: May 29, 2016     Accepted: August 26, 2016     Published: September 15, 2016

ABSTRACT

The blood-brain barrier (BBB) is the major clinical obstacle in the chemotherapeutic management of brain glioma. Here we synthesized a pH-sensitive dual-targeting doxorubicin (DOX) carrier to compromise tumor endothelial cells, enhance BBB transportation, and improve drug accumulation in glioma cells. The drug delivery system was constructed with polydopamine (PDA)-coated mesoporous silica nanoparticles (NPs, MSNs) and the PDA coating was functionalized with Asn-Gly-Arg (NGR), a ligand with specific affinity for cluster of differentiation 13 (CD13). MSN-DOX-PDA-NGR showed a higher intracellular accumulation in primary brain capillary endothelial cells (BCECs) and C6 cells and greater BBB permeability than the non-targeting NPs (MSN-DOX-PDA) did in vitro. Ex vivo and in vivo tests showed that MSN-DOX-PDA-NGR had a higher accumulation in intracranial tumorous tissue than the undecorated NPs did. Furthermore, the antiangiogenesis and antitumor efficacy of MSN-DOX-PDA-NGR were stronger than that of MSN-DOX-PDA. Therefore, these results indicate that the dual-targeting vehicles are potentially useful in brain glioma therapy.


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