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Nanomedicine engulfed by macrophages for targeted tumor therapy

Authors Li S, Feng S, Ding L, Liu Y, Zhu Q, Qian Z, Gu Y

Received 8 April 2016

Accepted for publication 19 June 2016

Published 23 August 2016 Volume 2016:11 Pages 4107—4124


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Lei Yang

Siwen Li,1,* Song Feng,1,* Li Ding,1 Yuxi Liu,1 Qiuyun Zhu,1 Zhiyu Qian,2 Yueqing Gu1

1Department of Biomedical Engineering, China Pharmaceutical University, 2Department of Biomedical Engineering, School of Automation, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

Abstract: Macrophages, exhibiting high intrinsic accumulation and infiltration into tumor tissues, are a novel drug vehicle for directional drug delivery. However, the low drug-loading (DL) capacity and the drug cytotoxicity to the cell vehicle have limited the application of macrophages in tumor therapy. In this study, different drugs involving small molecular and nanoparticle drugs were loaded into intrinsic macrophages to find a better way to overcome these limitations. Their DL capacity and cytotoxicity to the macrophages were first compared. Furthermore, their phagocytic ratio, dynamic distributions, and tumoricidal effects were also investigated. Results indicated that more lipid-soluble molecules and DL particles can be phagocytized by macrophages than hydrophilic ones. In addition, the N-succinyl-N'-octyl chitosan (SOC) DL particles showed low cytotoxicity to the macrophage itself, while the dynamic biodistribution of macrophages engulfed with different particles/small molecules showed similar profiles, mainly excreted from liver to intestine pathway. Furthermore, macrophages loaded with SOC–paclitaxel (PTX) particles exhibited greater therapeutic efficacies than those of macrophages directly carrying small molecular drugs such as doxorubicin and PTX. Interestingly, macrophages displayed stronger targeting ability to the tumor site hypersecreting chemokine in immunocompetent mice in comparison to the tumor site secreting low levels of chemokine in immunodeficiency mice. Finally, results demonstrated that macrophages carrying SOC–PTX are a promising pharmaceutical preparation for tumor-targeted therapy.

Keywords: macrophage, drug-loading capacity, SOC–PTX, tumor-targeted therapy

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