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A tumour microenvironment-responsive polymeric complex for targeted depletion of tumour-associated macrophages (TAMs)
Wang, Yu1; Guo, Guangxing2; Feng, Yanxian1; Long, Hongyan1; Ma, Dik-Lung3; Leung, Chung-Hang1; Dong, Lei2; Wang, Chunming1
2017-09-21
Source PublicationJOURNAL OF MATERIALS CHEMISTRY B
ISSN2050-750X
Volume5Issue:35Pages:7307-7318
Abstract

Tumour-associated macrophages (TAMs) play pivotal roles in promoting cancer progression. Systemic delivery of therapeutic agents to efficiently eliminate these cells remains challenging. Here, we report the development of a bio-responsive polymeric complex (P(3)AB) that can be systemically administrated to target and eliminate TAMs in tumours. This complex comprises a polymeric 'shell' and 'core'. The shell (PPP) consists of poly(ethylene glycol) (PEG), poly(lactic-co-glycolic acid) (PLGA), and a peptide that can be cleaved by matrix metalloproteases (MMPs) in the tumour microenvironment; and the 'core' (AB) is a bisphosphonate-glucomannan conjugate that has affinity for macrophage mannose receptors and selectively eliminates TAMs. Our data show that the P(3)AB complex can be accumulated in the tumour site thanks to its appropriate size and its PPP shell is sensitively cleaved by MMPs, efficiently releasing the AB core that can potently reduce TAM viability. The systemically delivered P(3)AB complex demonstrates favourable responses to the physiological features of the tumour microenvironment (e.g. underdeveloped vasculature and high MMP levels), and effectively inhibits tumour growth and restores local immuno-surveillance in vivo, without exerting hepatotoxicity. Taken together, our findings suggest that P(3)AB has the potential to be an effective and safe tool for TAM-targeting cancer immunotherapy.

DOI10.1039/c7tb01495c
URLView the original
Indexed BySCI
Language英语
WOS Research AreaMaterials Science
WOS SubjectMaterials Science, bioMaterials
WOS IDWOS:000411330100008
PublisherROYAL SOC CHEMISTRY
The Source to ArticleWOS
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Cited Times [WOS]:4   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorDong, Lei; Wang, Chunming
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China
2.State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China
3.Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Wang, Yu,Guo, Guangxing,Feng, Yanxian,et al. A tumour microenvironment-responsive polymeric complex for targeted depletion of tumour-associated macrophages (TAMs)[J]. JOURNAL OF MATERIALS CHEMISTRY B,2017,5(35):7307-7318.
APA Wang, Yu.,Guo, Guangxing.,Feng, Yanxian.,Long, Hongyan.,Ma, Dik-Lung.,...&Wang, Chunming.(2017).A tumour microenvironment-responsive polymeric complex for targeted depletion of tumour-associated macrophages (TAMs).JOURNAL OF MATERIALS CHEMISTRY B,5(35),7307-7318.
MLA Wang, Yu,et al."A tumour microenvironment-responsive polymeric complex for targeted depletion of tumour-associated macrophages (TAMs)".JOURNAL OF MATERIALS CHEMISTRY B 5.35(2017):7307-7318.
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