CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Liubing Li,Zenghui Gu,Yanxian Wu,Subin Lin,Xiaju Cheng,Leshuai W. Zhang,Jianzhong Qin,Qirong Dong,Yong Wang,Yangyun Wang
Combining radiotherapy with immunotherapy holds promise for treating solid tumors and metastases, but challenges persist, including hypoxia-induced immunosuppression and immune-related adverse events from off-target toxicity. To address this, we engineered an in-situ formed hydrogel by crosslinking hyaluronic acid and polyvinyl alcohol with a reactive oxygen species (ROS)-responsive linker (3-aminophenylboronic acid). This hydrogel leverages radiotherapy-induced ROS within the tumor microenvironment to trigger localized release of nitric oxide (NO) and the toll-like receptor 7/8 (TLR7/8) agonist R848. NO normalizes hypoxic tumor vasculature, while R848 amplifies radiotherapy-initiated antitumor immunity. In breast cancer and bone metastasis models, this radioimmune-regulated hydrogel significantly enhanced tumor normoxia, promoted dendritic cell maturation, and primed CD8 + T cells, substantially improving the efficacy of combined radioimmunotherapy. Our study highlights a potent hydrogel-based strategy to overcome key limitations in advanced cancer therapy.
研究领域:
肿瘤学
·
生物材料
·
免疫治疗
·
放射治疗
·
纳米医学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Zhenzhen Feng,Gui Chen,Min Zhong,Ling Lin,Ziyi Mai,Yan Tang,Guimei Chen,Wen Ma,Guang Li,Yuanyuan Yang,Zhiqiang Yu,Meng Yu
Pyroptosis is an inflammatory form of programmed cell death (PCD) that is regulated by the Gasdermin protein family in response to various stimuli, playing a critical role in the development of tumor therapy strategies. However, cancers are generally known to escape from PCD via immunosuppressive pathways or other resistant mechanisms. In this study, an acid-responsive Fe/Mn bimetal-organic framework nanosystem carrying metal ions and immune adjuvant R848 (FeMn@R@H) was designed for combining pyroptosis and augmented immunotherapy. The FeMn@R@H would be triggered to disintegrate and release Fe 3+ and Mn 2+ ions in response to the acidic tumor microenvironment (TME), thereby initiating Fenton-like reactions for ROS-mediated pyroptosis. On the one hand, the pyroptosis-caused cell rupture would induce the release of proinflammatory cytokines and immunogenic constituents from tumor cells, further resulting in immunogenic cell death (ICD) to promote antitumor immune responses. On the other hand, the co-delivered R848 could reverse suppressive tumor immune microenvironment (TIME) and induce inflammatory responses by activating the TLR7/8 pathway. In conclusion, this tumor-specific therapy system can co-deliver metal ions and R848 to tumor tissues to perform pyroptosis-mediated PCD and augmented anti-tumor immunotherapy.
研究领域:
癌症生物学
·
纳米技术
·
免疫治疗
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Zhijin Fan,Xiaoxiao Jiang,Tong Sun,Fanchu Zeng,Guojia Huang,Changhong Liang,Liming Nie
Tumor-associated macrophages (TAMs) are vital in the tumor microenvironment, contributing to immunosuppression and therapy tolerance. Despite their importance, the precise re-education of TAMs in vivo continues to present a formidable challenge. Moreover, the lack of real-time and efficient methods to comprehend the spatiotemporal kinetics of TAMs repolarization remains a significant hurdle, severely hampering the accurate assessment of treatment efficacy and prognosis. Herein, we designed a metal–organic frameworks (MOFs) based Caspase-1 nanoreporter (MCNR) that can deliver a TLR7/8 agonist to the TAMs and track time-sensitive Caspase-1 activity as a direct method to monitor the initiation of immune reprogramming. This nanosystem exhibits excellent TAMs targeting ability, enhanced tumor accumulation, and stimuli-responsive behavior. By inducing the reprogramming of TAMs, they were able to enhance T -cell infiltration in tumor tissue, resulting in inhibited tumor growth and improved survival in mice model. Moreover, MCNR also serves as an activatable photoacoustic and fluorescent dual-mode imaging agent through Caspase-1-mediated specific enzyme digestion. This feature enables non-invasive and real-time antitumor immune activation monitoring. Overall, our findings indicate that MCNR has the potential to be a valuable tool for tumor immune microenvironment remodeling and noninvasive quantitative detection and real-time monitoring of TAMs repolarization to immunotherapy in the early stage.
研究领域:
癌症生物学
·
免疫学
·
纳米技术
·
生物医学工程
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-20
·
IF 14.7
Liu Jinhu,Zhao Huajun,Gao Tong,Huang Xinyan,Liu Shujun,Liu Meichen,Mu Weiwei,Liang Shuang,Fu Shunli,Yuan Shijun,Yang Qinglin,Gu Panpan,Li Nan,Ma Qingping,Liu Jie,Zhang Xinke,Zhang Na,Liu Yongjun
Cytotherapy is a strategy to deliver modified cells to a diseased tissue, but targeting solid tumours remains challenging. Here we design macrophages, harbouring a surface glypican-3-targeting peptide and carrying a cargo to combat solid tumours. The anchored targeting peptide facilitates tumour cell recognition by the engineered macrophages, thus enhancing specific targeting and phagocytosis of tumour cells expressing glypican-3. These macrophages carry a cargo of the TLR7/TLR8 agonist R848 and INCB024360, a selective indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, wrapped in C16-ceramide-fused outer membrane vesicles (OMV) of Escherichia coli origin (RILO). The OMVs facilitate internalization through caveolin-mediated endocytosis, and to maintain a suitable nanostructure, C16-ceramide induces membrane invagination and exosome generation, leading to the release of cargo-packed RILOs through exosomes. RILO-loaded macrophages exert therapeutic efficacy in mice bearing H22 hepatocellular carcinomas, which express high levels of glypican-3. Overall, we lay down the proof of principle for a cytotherapeutic strategy to target solid tumours and could complement conventional treatment.
研究领域:
肿瘤学
·
免疫治疗
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Qingxu Song,Gongde Lan,Qian Li,Yang Lin,Xin Chen,Hong Liu,Yufeng Cheng,Yuxia Luan
Hypofractionated radiotherapy (HRT) is a promising approach for tumor treatment, owing to its straightforward elimination of tumor cells and stimulation of immunogenic cell death. However, clinical application of HRT is hindered by the inherent radio-resistance and inadequate immune activation. Herein, an injectable hydrogel platform was reported, enabling a cascade amplification of radiosensitization and immune activation to potentiate HRT. The hydrogel with encapsulated TLR7/8 agonist R848 is in situ constructed in tumor via L-norvaline-based polymer (LNP, a gelator). During HRT, the released L-norvaline from LNP suppresses L-arginine consumption through arginase 1 (ARG1) pathway, sparing adequate L-arginine that was used for radiosensitizer nitric oxide (NO) production by inducible NO synthase (iNOS). Meanwhile, R848 repolarizes tumor-associated macrophages (TAMs) from M2 type with rich ARG1 to M1 type with rich iNOS, reinforcing NO production and disrupting M2-type TAMs-induced radio-resistance and immunosuppression. Therefore, the hydrogel demonstrates a cascade regulation of radio-sensitization and immune activation, achieving powerful inhibition of tumor growth and tumor metastasis. This hydrogel provides a novel approach to potentiate HRT, holding great promise in clinical application.
研究领域:
肿瘤学
·
放射肿瘤学
·
免疫疗法
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2021
·Vol. 10
·期 21
·2101222
·
IF 9.933
Peng Yan,Yang Luo,Xinyang Li,Yingmin Li,Yi Wang,Jian Wu,Shaobing Zhou
In situ vaccination can trigger an antitumor immune response. However, the therapeutic effect is still limited since the high expression of adenosine binding to G protein-coupled receptor A2AR induces an immunosuppressive effect. In this work, a new formulation is presented with the combination of a nanovaccine based on redox-responsive polymer micelles and A2AR antagonist SCH58261. The micelles simultaneously encapsulate immunogenic cell death (ICD) inducer doxorubicin (DOX) and adjuvant toll-like receptor 7 and 8 (TLR7/8) agonist R848, acting as the potent in situ vaccines. A high concentration of glutathione in tumor cells leads to the disintegration of these micelles, releasing DOX and R848 to mediate ICD, inducing the activation of dendritic cells and initiating an immune response. Meanwhile, A2AR antagonist SCH58261, a generation immune checkpoint blocker, inhibits the immunosuppressive adenosinergic pathway in the tumor microenvironment, activating natural killer (NK) cells and CD8 + T cells, and inhibiting the proliferation of regulatory T cells. Therefore, this formulation can trigger a robust systemic antitumor immune response.
研究领域:
癌症研究
·
免疫学
·
纳米医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Heying Chen,Xiaomeng Cai,Jiayu Zhang,Hongyan Sun,Jie Zhang,Jun Chen,Zhenglin Yang,Dongqing Wang
Combination of chemotherapy and cancer immunotherapy has shown substantial clinical promise. However, the immunosuppressive tumor microenvironment (TME) poses a critical barrier to this combination therapy. Here, a tumor lysosome-targeted immunomodulatory strategy based on a biomimetic nanoadjuvant is presented, which effectively overcomes the immunosuppressive TME and demonstrates enhanced therapeutic efficacy when combined with chemotherapy. This nanoadjuvant integrates Fe-DOX coordination nanoparticles, a MnCO 3 shell, TLR7/8 agonist (R848), and a mature dendritic cell membrane (DCM) coating. The resulting DCM@(Fe-DOX-Mn-R848) nanoadjuvant induces immunogenic cell death in tumor cells via lysosomal-mitochondrial cascade destruction. Concurrently, it activates the cGAS-STING signaling pathway to promote dendritic cell maturation and repolarize tumor-associated macrophages from M2 to M1 phenotype, thereby effectively enhancing CD8 + T cell activation and tumor therapeutic efficacy. When combined with PD-L1 blockade therapy, the nanoadjuvant demonstrates enhanced efficacy in murine models of primary and recurrent triple-negative breast cancer, establishing durable immune memory. This platform demonstrates significant potential in overcoming immunosuppressive TME and advancing combination therapy through lysosome-targeting drug delivery technology, revealing promising prospects for cancer treatment.
研究领域:
纳米医学
·
免疫学
·
癌症生物学
·
生物工程
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small Methods
·
2023
·Vol. 7
·期 5
·2201327
·
IF 12.4
Xinyang Li,Yang Luo,Zhengjie Huang,Yi Wang,Jian Wu,Shaobing Zhou
In the treatment of solid tumors, the complex barriers composed of cancer-associated fibroblasts (CAFs) prevent drug delivery and T cells infiltration into tumor tissues. Although nanocarriers hold great prospects in drug delivery, fibrosis causes the biological barrier and immunosuppressive tumor microenvironment (ITM) that impairs the anti-tumor efficacy of nanocarriers. Here, a small dendritic macromolecule loaded with doxorubicin (PAMAM-ss-DOX) (DP) is synthesized and encapsulated into pH-responsive nanoliposome, together with adjuvant toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) and losartan (LOS). The pH-responsive liposome facilitates the simultaneous and effective delivery of DP, R848, and LOS, which can decompose and release these drugs under the acidic tumor microenvironment. The small sized DP (≈25 nm) with the ability to penetrate into tumor tissue and immunogenic cell death (ICD) can reverse the ITM and elicit immune response, which is equivalent to the effect of an in situ vaccine. Moreover, LOS reduces the activity of CAFs effectively, which can contribute to the infiltration of T cells. Therefore, this nano-platform provides a new therapeutic strategy for enhanced chemo-immunotherapy.
研究领域:
肿瘤学
·
药学
·
免疫学
·
纳米技术
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）