Nanomedicine engulfed by macrophages for targeted tumor therapy

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...

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Main Authors:	Li, Siwen, Feng, Song, Ding, Li, Liu, Yuxi, Zhu, Qiuyun, Qian, Zhiyu, Gu, Yueqing
Format:	Online
Language:	English
Published:	Dove Medical Press 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003564/

id	pubmed-5003564
recordtype	oai_dc
spelling	pubmed-50035642016-09-06 Nanomedicine engulfed by macrophages for targeted tumor therapy Li, Siwen Feng, Song Ding, Li Liu, Yuxi Zhu, Qiuyun Qian, Zhiyu Gu, Yueqing Original Research 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. Dove Medical Press 2016-08-23 /pmc/articles/PMC5003564/ /pubmed/27601898 http://dx.doi.org/10.2147/IJN.S110146 Text en © 2016 Li et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Li, Siwen Feng, Song Ding, Li Liu, Yuxi Zhu, Qiuyun Qian, Zhiyu Gu, Yueqing
spellingShingle	Li, Siwen Feng, Song Ding, Li Liu, Yuxi Zhu, Qiuyun Qian, Zhiyu Gu, Yueqing Nanomedicine engulfed by macrophages for targeted tumor therapy
author_facet	Li, Siwen Feng, Song Ding, Li Liu, Yuxi Zhu, Qiuyun Qian, Zhiyu Gu, Yueqing
author_sort	Li, Siwen
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
description	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.
publisher	Dove Medical Press
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003564/
_version_	1613638395537391616

Nanomedicine engulfed by macrophages for targeted tumor therapy

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