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Targeted depletion of tumour-associated macrophages by an alendronate-glucomannan conjugate for cancer immunotherapy
Zhan X.1; Jia L.2; Niu Y.1; Qi H.2; Chen X.1; Zhang Q.1; Zhang J.2; Wang Y.1; Dong L.2; Wang C.1
2014
Source PublicationBiomaterials
ISSN1429612
Volume35Issue:38Pages:10046
Abstract

Tumour-associated macrophages (TAMs) are a set of macrophages residing in the tumour microenvironment. They play essential roles in mediating tumour angiogenesis, metastasis and immune evasion. Delivery of therapeutic agents to eliminate TAMs can be a promising strategy for cancer immunotherapy but an efficient vehicle to target these cells is still in pressing need. In this study, we developed a bisphosphonate-glucomannan conjugate that could efficiently target and specifically eliminate TAMs in the tumour microenvironment. We employed the polysaccharide from Bletilla striata (BSP), a glucomannan affinitive for macrophages that express abundant mannose receptors, to conjugate alendronate (ALN), a bisphosphonate compound with invitro macrophage-inhibiting activities. In both invitro and invivo tests, the prepared ALN-BSP conjugate could preferentially accumulate in macrophages and induced them into apoptosis. In the subcutaneous S180 tumour-bearing mice model, the treatment using ALN-BSP effectively eliminated TAMs, remarkably inhibited angiogenesis, recovered local immune surveillance, and eventually suppressed tumour progression, without eliciting any unwanted effect such as systematic immune response. Interestingly, ALN alone failed to exhibit any anti-TAM activity invivo, probably because this compound was susceptible to the mildly acidic tumour microenvironment. Taken together, these results demonstrate the potential of ALN-BSP as a safe and efficient tool targeted at direct depletion of TAMs for cancer immunotherapy. © 2014 Elsevier Ltd.

KeywordBisphosphonate Bletilla Striata Polysaccharide Cancer Immunotherapy Glucomannan Macrophage Mannose Receptor Tumour-associated Macrophages
DOI10.1016/j.biomaterials.2014.09.007
URLView the original
Indexed BySCI
Language英语
WOS Research AreaMaterials Science
WOS SubjectEngineering, Biomedical ; Materials Science, bioMaterials
WOS IDWOS:000344207100006
The Source to ArticleScopus
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Cited Times [WOS]:56   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorDong L.; Wang C.
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, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Zhan X.,Jia L.,Niu Y.,et al. Targeted depletion of tumour-associated macrophages by an alendronate-glucomannan conjugate for cancer immunotherapy[J]. Biomaterials,2014,35(38):10046.
APA Zhan X..,Jia L..,Niu Y..,Qi H..,Chen X..,...&Wang C..(2014).Targeted depletion of tumour-associated macrophages by an alendronate-glucomannan conjugate for cancer immunotherapy.Biomaterials,35(38),10046.
MLA Zhan X.,et al."Targeted depletion of tumour-associated macrophages by an alendronate-glucomannan conjugate for cancer immunotherapy".Biomaterials 35.38(2014):10046.
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