Nanoscale Horizons
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2025
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IF 6.6
Si-Ye Tong,Cong-Min Huo,Yu-Cheng Zuo,Shuo Gao,David Tai Leong,Wei Xue,Jing-Yi Zhu
Immunosuppression from the tumor microenvironment plays a key role in the failure of cancer immunotherapy. The presence of potassium ions (K+) from dying tumor cells creates an immunosuppressive environment that encourages tumor-associated macrophages (TAMs) to adopt a pro-tumor M2-like phenotype. Alleviating immune suppression from the high K+ environment might boost innate immunity and fight tumor growth. Herein, disulfide-rich mesoporous silica modified with 18-crown-6 ether was developed as a nanocarrier (D-C) to load ML133, encapsulating with the DiR-embedded macrophage membrane (CM) to create D-C/M@CM/DiR. We first saturated the phagocytosis of the mononuclear phagocyte system (MPS) with blank nanocarriers to enhance the tumor accumulation of D-C/M@CM/DiR, which was coated with the same CM. 18-Crown-6 ether captures K+ to reduce immunosuppression, while ML133 promotes the polarization of TAMs to an anti-tumor M1 phenotype by targeting the K+ channel protein Kir2.1 on their membranes. This strategy activates the anti-tumor immune response and effectively inhibits tumor growth.
研究领域:
肿瘤学
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免疫学
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
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IF 4.7
Liya Feng,Yuanxin Wang,Xiangyue Wang,Baochan Li,Yifan Liu,Wanying Zhang,Jianbo Ji,Lijun Shao,Xiuli Guo
In the tumor microenvironment (TME), tumor associated macrophages (TAMs) often exhibit a preference for M2-like phenotype, which supports tumor progression under hypoxia. The underlying mechanisms driving the behavior of hypoxic TAMs are highly complex. Recently, exosomal long non-coding RNAs (lncRNAs) derived from non-cancerous cells within TME have attracted more attention from researchers. In the present study, we investigated the function of exosomal lncRNA MIR210HG derived from hypoxic TAMs in triple negative breast cancer (TNBC). Results showed that MIR210HG was significantly upregulated in hypoxic TAMs, their exosomes, and exosomes-treated TNBC cells. When MIR210HG was suppressed, the expression of M2-polarization markers and proteins associated with the PI3K/Akt/mTOR pathway in hypoxic TAMs was notably inhibited. Moreover, the suppression of TAM-derived exosomal MIR210HG effectively inhibited the migration, invasion and vasculogenic mimicry (VM) formation of TNBC cells. Notably, dual inhibition of both exosomal and endogenous MIR210HG in tumor cells synergistically restricted TNBC metastasis of in vivo . Mechanistically, we elucidated that MIR210HG promoted the malignant phenotypes of TNBC by upregulating the expression of HIF-1α protein, which in turn initiated RASSF7 transcription, resulting in the promotion of epithelial-mesenchymal transition (EMT) process. Collectively, our results identified MIR210HG as a key molecule mediating exosome-based communication from hypoxic TAMs to TNBC cells and revealed its pro-metastatic role, Consequently, MIR210HG emerges as a highly promising therapeutic target of TNBC.
研究领域:
癌症生物学
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分子生物学
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免疫学
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细胞生物学
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遗传学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Xiao Zheng,Ying Liu,Yiqiong Liu,Jie Zang,Kun Wang,Zichen Yang,Nana Chen,Jiuyuan Sun,Li Huang,Yan Li,Liangyi Xue,Hui Zhi,Xiaoyou Zhang,Min Yu,Shiyu Chen,Haiqing Dong,Yongyong Li
Repolarizing the tumor-associated macrophages (TAMs) towards the antitumoral M1-like phenotype has been a promising approach for cancer immunotherapy . However, the anti-cancer immune response is severely limited mainly by the repolarized M1-like macrophages belatedly returning to the M2-like phenotype (i.e., negative feedback). Inspired by nitric oxide (NO) effectively preventing repolarization of inflammatory macrophages in inflammatory diseases, herein, we develop an arginine assembly, as NO nano-donor for NO generation to prevent the negative feedback of the macrophage repolarization. The strategy is to first apply reversible tagging of hydrophobic terephthalaldehyde to create an arginine nano-assembly, and then load a toll-like receptor 7/8 agonist resiquimod (R848) (R848@Arg). Through this strategy, a high loading efficiency of 40 % for the arginine and repolarization characteristics for TAMs can be achieved. Upon the macrophage repolarization by R848, NO can be intracellularly generated from the released arginine by the upregulated inducible nitric oxide synthase. Mechanistically, NO effectively prevented the negative feedback of the repolarized macrophage by mitochondrial dysfunction via blocking oxidative phosphorylation . Notably, R848@Arg significantly increased the tumor inhibition ratio by 3.13-fold as compared to the free R848 by maintaining the M1-like phenotype infiltrating into tumor. The Arg-assembly as NO nano-donor provides a promising method for effective repolarization of macrophages.
研究领域:
癌症免疫学
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药理学
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纳米技术
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免疫治疗
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Nanotechnology
·
2024
·
IF 38.1
Qin Jiaqi,Liu Jingjie,Wei Zhaohan,Li Xin,Chen Zhaoxia,Li Jianye,Zheng Wenxia,Liu Haojie,Xu Shiyi,Yong Tuying,Zhao Ben,Gou Shanmiao,Ju Shenghong,Teng Gao-Jun,Yang Xiangliang,Gan Lu
Nerve–cancer crosstalk has gained substantial attention owing to its impact on tumour growth, metastasis and therapy resistance. Effective therapeutic strategies targeting tumour-associated nerves within the intricate tumour microenvironment remain a major challenge in pancreatic cancer. Here we develop Escherichia coli Nissle 1917-derived outer membrane vesicles conjugated with nerve-binding peptide NP41, loaded with the tropomyosin receptor kinase (Trk) inhibitor larotrectinib (Lar@NP-OMVs) for tumour-associated nerve targeting. Lar@NP-OMVs achieve efficient nerve intervention to diminish neurite growth by disrupting the neurotrophin/Trk signalling pathway. Moreover, OMV-mediated repolarization of M2-like tumour-associated macrophages to an M1-like phenotype results in nerve injury, further accentuating Lar@NP-OMV-induced nerve intervention to inhibit nerve-triggered proliferation and migration of pancreatic cancer cells and angiogenesis. Leveraging this strategy, Lar@NP-OMVs significantly reduce nerve infiltration and neurite growth promoted by gemcitabine within the tumour microenvironment, leading to augmented chemotherapy efficacy in pancreatic cancer. This study sheds light on a potential avenue for nerve-targeted therapeutic intervention for enhancing pancreatic cancer therapy.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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