Targeted depletion of tumour-associated macrophages by an alendronate–glucomannan conjugate for cancer immunotherapy

Zhan, Xiudan; Jia, Lixin; Niu, Yiming; Qi, Haixia; Chen, Xiuping; Zhang, Qingwen; Zhang, Junfeng; Wang, Ying; Dong, Lei; Wang, Chunming

doi:10.1016/j.biomaterials.2014.09.007

Cited by 137 publications

(85 citation statements)

References 49 publications

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“…TAMs (defined as CD45 + CD11b + CD64 + F4/80 + cells) are recognized as M2-polarized macrophages abundantly expressing M2-specific markers such as Arg1, CD206 and high levels of vascular endothelial growth factor (Vegf) (31, 45). To determine aerobic glycolysis on TAMs, we subcutaneously injected 1 × 10 6 B16 cells, intraperitoneally injected 2-DG from day 9 and harvested on day 19.…”

Section: Resultsmentioning

confidence: 99%

2-Deoxy-d-Glucose Treatment Decreases Anti-inflammatory M2 Macrophage Polarization in Mice with Tumor and Allergic Airway Inflammation

et al. 2017

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As important effector cells in inflammation, macrophages can be functionally polarized into either inflammatory M1 or alternatively activated anti-inflammatory M2 phenotype depending on surroundings. The key roles of glycolysis in M1 macrophage polarization have been well defined. However, the relationship between glycolysis and M2 polarized macrophages is still poorly understood. Here, we report that 2-deoxy-d-glucose (2-DG), an inhibitor of the glycolytic pathway, markedly inhibited the expressions of Arg, Ym-1, Fizz1, and CD206 molecules, the hall-markers for M2 macrophages, during macrophages were stimulated with interleukin 4. The impacted M2 macrophage polarization by 2-DG is not due to cell death but caused by the impaired cellular glycolysis. Molecular mechanism studies indicate that the effect of 2-DG on M2 polarized macrophages relies on AMPK-Hif-1α-dependent pathways. Importantly, 2-DG treatment significantly decreases anti-inflammatory M2 macrophage polarization and prevents disease progression in a series of mouse models with chitin administration, tumor, and allergic airway inflammation. Thus, the identification of the master role of glycolysis in M2 macrophage polarization offers potential molecular targets for M2 macrophages-mediated diseases. 2-DG therapy may have beneficial effects in patients with tumors or allergic airway inflammation by its negative regulation on M2 macrophage polarization.

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Section: Resultsmentioning

confidence: 99%

2-Deoxy-d-Glucose Treatment Decreases Anti-inflammatory M2 Macrophage Polarization in Mice with Tumor and Allergic Airway Inflammation

et al. 2017

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“…Additionally, to confi rm the effi cacy of the conjugated particle compared to free alendronate in vivo, ALN-BSP was shown to decrease vascular endothelial growth factor (VEGF) levels by 83.9 % and MMP-9 by 65.3 %, compared to free alendronate. These markers are directly involved in promoting tumor growth and metastasis, and thus, ALN-BSP showed anti-tumorigenic effects [ 49 ].…”

Section: Active Macrophage Targetingmentioning

confidence: 99%

“…Actively targeting macrophages in cancer models has become a popular therapeutic method because macrophages play a signifi cant role in promoting growth and metastasis of tumors [ 49 ]. Tumors are able to recruit monocytes and macrophages to the cancerous site by releasing of a cascade of chemoattractants.…”

Section: Active Macrophage Targetingmentioning

confidence: 99%

Nanoparticulate Systems for Controlling Monocyte/Macrophage Behavior

Pentecost

Lurier

Spiller

2016

Microscale Technologies for Cell Engineering

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“…Similar to the latter study, the polysaccharide mannan, a ligand for the mannose receptor, has been used in several studies for the delivery of nanoparticles to macrophages [156,157]. In a study by Zhan et al, a glucomannan polysaccharide from Bletilla striata was employed to target the mannose receptor [158]. The polysaccharide was coupled to the bisphosphonate alendronate for the depletion of macrophages.…”

Section: Passive and Active Targetingmentioning

confidence: 99%

Nanomedicine Strategies to Target Tumor-Associated Macrophages

Binnemars-Postma

Storm

Prakash

2017

IJMS

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In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different subtypes, each of which has a different function. While classically activated M1 macrophages are involved in inflammatory and malignant processes, activated M2 macrophages are more involved in the wound-healing processes occurring in tumors. Tumor-associated macrophages (TAM) display M2 macrophage characteristics and support tumor growth and metastasis by matrix remodeling, neo-angiogenesis, and suppressing local immunity. Due to their detrimental role in tumor growth and metastasis, selective targeting of TAM for the treatment of cancer may prove to be beneficial in the treatment of cancer. Due to the plastic nature of macrophages, their activities may be altered to inhibit tumor growth. In this review, we will discuss the therapeutic options for the modulation and targeting of TAM. Different therapeutic strategies to deplete, inhibit recruitment of, or re-educate TAM will be discussed. Current strategies for the targeting of TAM using nanomedicine are reviewed. Passive targeting using different nanoparticle systems is described. Since TAM display a number of upregulated surface proteins compared to non-TAM, specific targeting using targeting ligands coupled to nanoparticles is discussed in detail.

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Targeted depletion of tumour-associated macrophages by an alendronate–glucomannan conjugate for cancer immunotherapy

Cited by 137 publications

References 49 publications

2-Deoxy-d-Glucose Treatment Decreases Anti-inflammatory M2 Macrophage Polarization in Mice with Tumor and Allergic Airway Inflammation

2-Deoxy-d-Glucose Treatment Decreases Anti-inflammatory M2 Macrophage Polarization in Mice with Tumor and Allergic Airway Inflammation

Nanoparticulate Systems for Controlling Monocyte/Macrophage Behavior

Nanomedicine Strategies to Target Tumor-Associated Macrophages

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