Research Papers:

Exploiting macrophages as targeted carrier to guide nanoparticles into glioma

Liang Pang, Jing Qin, Limei Han, Wenjie Zhao, Jianming Liang, Zhongyi Xie, Pei Yang and Jianxin Wang _

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Oncotarget. 2016; 7:37081-37091. https://doi.org/10.18632/oncotarget.9464

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Liang Pang1, Jing Qin1, Limei Han1, Wenjie Zhao2, Jianming Liang1, Zhongyi Xie1, Pei Yang1, Jianxin Wang1

1Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China

2Shanghai Institute of Pharmaceutical Industry, Shanghai, 201203, China

Correspondence to:

Jianxin Wang, email: [email protected]

Keywords: macrophages, glioma, inflammation, hypoxic, nanoparticles

Received: October 18, 2015     Accepted: April 24, 2016     Published: May 18, 2016


The restriction of anti-cancer drugs entry to tumor sites in the brain is a major impediment to the development of new strategies for the treatment of glioma. Based on the finding that macrophages possess an intrinsic homing property enabling them to migrate to tumor sites across the endothelial barriers in response to the excretion of cytokines/chemokines in the diseased tissues, we exploited macrophages as ‘Trojan horses’ to carry drug-loading nanoparticles (NPs), pass through barriers, and offload them into brain tumor sites. Anticancer drugs were encapsulated in nanoparticles to avoid their damage to the cells. Drug loading NPs was then incubated with RAW264.7 cells in vitro to prepare macrophage-NPs (M-NPs). The release of NPs from M-NPs was very slow in medium of DMEM and 10% FBS and significantly accelerated when LPS and IFN-γ were added to mimic tumor inflammation microenvironment. The viability of macrophages was not affected when the concentration of doxorubicin lower than 25 μg/ml. The improvement of cellular uptake and penetration into the core of glioma spheroids of M-NPs compared with NPs was verified in in vitro studies. The tumor-targeting efficiency of NPs was also significantly enhanced after loading into macrophages in nude mice bearing intracranial U87 glioma. Our results provided great potential of macrophages as an active biocarrier to deliver anticancer drugs to the tumor sites in the brain and improve therapeutic effects of glioma.

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