Nanomedicine engulfed by macrophages for targeted tumor therapy

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&...

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Autores principales: Li S, Feng S, Ding L, Liu Y, Zhu Q, Qian Z, Gu Y
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Lenguaje:EN
Publicado: Dove Medical Press 2016
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Acceso en línea:https://doaj.org/article/3774101837534cfe83cad524715380b8
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spelling oai:doaj.org-article:3774101837534cfe83cad524715380b82021-12-02T05:36:20ZNanomedicine engulfed by macrophages for targeted tumor therapy1178-2013https://doaj.org/article/3774101837534cfe83cad524715380b82016-08-01T00:00:00Zhttps://www.dovepress.com/nanomedicine-engulfed-by-macrophages-for-targeted-tumor-therapy-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Siwen 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 therapyLi SFeng SDing LLiu YZhu QQian ZGu YDove Medical Pressarticlemacrophagedrug capacitySOC-PTXtumor targeted therapy.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 4107-4124 (2016)
institution DOAJ
collection DOAJ
language EN
topic macrophage
drug capacity
SOC-PTX
tumor targeted therapy.
Medicine (General)
R5-920
spellingShingle macrophage
drug capacity
SOC-PTX
tumor targeted therapy.
Medicine (General)
R5-920
Li S
Feng S
Ding L
Liu Y
Zhu Q
Qian Z
Gu Y
Nanomedicine engulfed by macrophages for targeted tumor therapy
description 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
format article
author Li S
Feng S
Ding L
Liu Y
Zhu Q
Qian Z
Gu Y
author_facet Li S
Feng S
Ding L
Liu Y
Zhu Q
Qian Z
Gu Y
author_sort Li S
title Nanomedicine engulfed by macrophages for targeted tumor therapy
title_short Nanomedicine engulfed by macrophages for targeted tumor therapy
title_full Nanomedicine engulfed by macrophages for targeted tumor therapy
title_fullStr Nanomedicine engulfed by macrophages for targeted tumor therapy
title_full_unstemmed Nanomedicine engulfed by macrophages for targeted tumor therapy
title_sort nanomedicine engulfed by macrophages for targeted tumor therapy
publisher Dove Medical Press
publishDate 2016
url https://doaj.org/article/3774101837534cfe83cad524715380b8
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AT zhuq nanomedicineengulfedbymacrophagesfortargetedtumortherapy
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