CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Yaru Zhang,Wenyu Xie,Jiamin Luo,Rui Gao,Zhimin Gao,Xinyi Wang,Yongxin Huang,Chen Lin,Meiling Tan,Zhiyao Hou
Effectively activating macrophages to engulf tumor cells has attracted intensive attention in cancer immunotherapy. However, tumor cells can upregulate anti-phagocytic signals (such as CD47 molecules) to bind with signal regulatory protein-α (SIRPα), ultimately providing a “don’t eat me” signal to evade phagocytosis. Blockading CD47 alone is insufficient to stimulate macrophages phagocytosis due to the absence of endogenous activating signals (“eat me” signal). Herein, a mesoporous silica (MSN) modified by Cu 9 S 5 nanoparticle with mimicking enzyme activities were synthesized and utilized to electrostatically load the anti-CD47 antibodies (aCD47), generating MCC nanozymes, to improve macrophage-mediated cancer immunotherapy. MCC nanozymes can target tumor cells by specifically binding to the cell-surface CD47, disabling the “don’t eat me” signal. Meanwhile, under near infrared light (1064 nm) stimulation, MCC nanozymes exhibit the enhanced glutathione oxidase-like and peroxidase-like enzymatic activities by the photothermal effect, which lead the reactive oxygen species (ROS) generation to induce endoplasmic reticulum (ER) stress amplification, resulting the exposure of calreticulin (CALR) for providing the endogenous “eat-me” signals to macrophages. In a 4T1 breast cancer model, even under mild photothermal condition, MCC nanozymes effectively inhibit tumor growth and metastasis. Collectively, this dual-regulatory strategy presents a promising approach for macrophage-mediated cancer immunotherapy.
研究领域:
肿瘤学
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
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IF 19
Haoting Chen,Ding Yang,Dongyue He,Zechuan Li,Gengyou Li,Jing Ma,Jiaqing Wan,Meifen Luo,Qi Chen,Yansong Liu,Qihan Zhang,Yanwen Liang,Ying-Shi Sun,Weisheng Guo,Lu Liu
Immune checkpoint blockade (ICB) therapies have transformed the management of metastatic and advanced malignancies. A novel therapeutic paradigm targeting CD47 has emerged as a promising approach to enhance macrophage-mediated tumor phagocytosis; however, systemic toxicity stemming from nonspecific antibody distribution remains a critical clinical challenge. To address this limitation, a modular nanoparticle system, termed Differentiation Responsive Architected Macrophage (DREAM), was engineered to exploit intrinsic macrophage homing for tumor-specific co-delivery of anti-CD47 antibodies (aCD47) and Resiquimod (R848). This platform circumvents reliance on tumor microenvironment-derived matrix metalloproteinase-9 (MMP-9) by utilizing autocrine MMP-9 secretion to initiate spatially controlled drug release, while simultaneously amplifying protease production via dynamic macrophage differentiation. In vitro analyses demonstrated stimulus-responsive payload dissociation kinetics. In vivo evaluation in murine tumor models revealed that systemic DREAM administration induced robust tumor regression following three treatment cycles, concomitant with a shift in immune microenvironment polarization from an immunosuppressive to pro-inflammatory phenotype. By integrating autonomous activation mechanisms with cell-specific targeting, this strategy establishes a macrophage-centric delivery platform that enhances therapeutic precision, mitigates off-tissue toxicity, and augments antitumor efficacy, thereby advancing the translational potential of next-generation ICB modalities.
研究领域:
肿瘤学
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免疫学
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2022
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IF 11.467
Qian Chen,Yanan Li,Shuai Zhou,Dali Chen,Muye Zhou,Qinying Chen,Yuren Lu,Naicong Cai,Can Liu,Yumeng Guo,Zijie Qiu,Xiaoyan Hou,Jiasheng Tu,Weiyang Shen,Chunmeng Sun
Postsurgical treatment is of great importance to combat tumor recurrence and metastasis. Anti-CD47 antibodies (aCD47) can block the CD47-signal regulatory protein-alpha (CD47-SIRPα) pathway to restore immunity. Here, an in-situ gel implantation was engineered by crosslinking chitosan (CS) and pullulan (Pul) for postsurgical treatment. A highly selected chemotherapeutic, cyclopamine (Cyc), encapsulated in liposomes (Cyc-Lip) was co-loaded with aCD47 in gels for chemoimmunotherapy. Importantly, a sequential drug release kinetics can be achieved. Nanotherapeutics were confirmed to be released prior to aCD47 in a burst-release manner, which was benefit for immediately killing residual tumor cells followed by releasing tumor antigens . Meanwhile, aCD47 was released in a sustained-release manner to restore macrophage functions and exert anti-tumor immune responses. Afterwards, the efficacy of in-situ chemoimmunotherapy was confirmed on 4T1 mouse breast cancer models, which could not only efficiently augment anti-tumor effect to inhibit tumor recurrence but also establish a long-term immune memory to combat tumor metastasis.
研究领域:
肿瘤学
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生物材料学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2023
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IF 10.8
Lu Ye,Wei Lv,Weichong He,Shengnan Li,Zhiyi Min,Le Gong,Qi Zhang,Chuanhui Teng,Shanbo Sun,Lingyan Lv,Yi Guo,Hongliang Xin
Infiltrative glioma growth makes surgical excision incomplete, and the residual tumor cells proliferate rapidly. Residual glioma cells evade phagocytosis by macrophages through upregulating anti-phagocytosis molecule CD47, which binds to the signal regulatory protein alpha (SIRPα) of macrophages. Specifically, blocking the CD47-SIRPα pathway is a potential strategy for post-resection glioma treatment. In addition, the anti-CD47 antibody (α-CD47) in combination with temozolomide (TMZ) caused an enhanced pro-phagocytic effect due to the TMZ not only destroying DNA but also inducing endoplasmic reticulum stress response of glioma cells. However, the obstruction of the blood-brain barrier makes systemic combination therapy not ideal for post-resection glioma treatment. Herein, we designed a temperature-sensitive hydrogel system based on a moldable thermosensitive hydroxypropyl chitin (HPCH) copolymer to encapsulate both α-CD47 and TMZ as α-CD47& [email protected] for in situ postoperative cavity administration. Through the in vitro and in vivo evaluations, α-CD47& [email protected] significantly inhibited glioma recurrence post-resection through enhancement of pro-phagocytosis of macrophages, recruitment, and activation of CD8 + T cells and NK cells.
研究领域:
肿瘤学
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药理学
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生物医学工程
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免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2022
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IF 10.633
Afeng Yang,Shupei Sheng,Yun Bai,Guozheng Xing,Xuya Yu,Dunwan Zhu,Lin Mei,Xia Dong,Feng Lv
Vascular abnormalities are directly related to the tumor immunosuppressive microenvironment, which is an important obstacle to effective immunotherapy. The combination of antiangiogenesis therapy and immunotherapy may promote a mutually reinforcing cycle of immune reprogramming and vascular normalization to increase the effectiveness of immunotherapy. Herein, a hydrogel/nanosystem-mediated antiangiogenesis combined immunotherapy strategy was used to regulate the tumor microenvironment by the controlled release of apatinib, CD47 antibody (aCD47), and CpG. The combination of hydrogel with nanoparticles protected drug activity and maintained a long-term slow release of the drug for maximum synergistic efficacy. Apatinib promotes vascular normalization in tumors and enhances the efficacy of aCD47-based immunotherapy. The addition of immunoadjuvant CpG further enhanced antigen presentation and stimulated the anti-tumor activity of macrophages to strengthen the efficacy of antiangiogenesis combined immunotherapy. The main effector immune cells , including CD4 + T , CD8 + T , NK, and activity DCs, were significantly increased after combination treatment, while the proportion of various immunosuppressive cells decreased significantly, especially MDSCs and M2-polarized macrophages. Based on an effective systemic immune response, the hydrogel/nanoparticle-mediated cooperative combination of antiangiogenesis and immunotherapy enhanced the synergistic effect for primary tumors and prevented metastasis for tumor treatment. The biomaterial-mediated antiangiogenesis combined immunotherapy strategy is a promising strategy for effective immunotherapy. Statement of significance Relieving immunosuppression of the tumor microenvironment is the key to restoring and rebuilding the normal anti-tumor immune defense of the body. Vascular abnormalities are directly related to the tumor immunosuppressive microenvironment, which is an important obstacle to effective immunotherapy. The combination of antiangiogenesis and immunotherapy may promote a mutually reinforcing cycle of immune reprogramming and vascular normalization to increase the effectiveness of immunotherapy. For the combination of antiangiogenesis and immunotherapy, effective drug delivery to overcome local immune tolerance and regulate the tumor microenvironment to increase therapeutic effects is an important issue. The hydrogel/nanomaterial composite system constructs a dual sustained-release system to achieve step-by-step controlled release of antiangiogenic drugs and immune immunotherapy drugs to promote cooperative combination therapy.
研究领域:
肿瘤学
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药学
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纳米技术
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免疫学
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药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
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IF 3.973
Zhaoming Guo,Ye Liu,Hao Zhou,Kun Zheng,Dong Wang,Mingli Jia,Pengcheng Xu,Kun Ma,Changhao Cui,Li Wang
CD47 , a transmembrane protein overexpressed in most tumors, limits macrophage phagocytosis by interacting with macrophage signal-regulated protein α (SIRPα). In this study, we have developed CD47-targeted bismuth selenide nanoparticles (Ab-PEG-Bi 2 Se 3 ) that increase phagocytosis of cancer cells by macrophages to actualize improved photothermal therapy (PTT). The functionalized nanoparticles were constructed by conjugating anti-CD47 antibody (Ab) to PEGylated bismuth selenide nanoparticles (PEG-Bi 2 Se 3 ). The anti-CD47 antibody modified on the nanoparticles enhanced the phagocytic activity of macrophages toward tumor cells by specifically blocking the crosstalk between CD47 and SIRPα. Meanwhile, Ab-PEG-Bi 2 Se 3 showed excellent photothermal performance including strong near infrared (NIR) absorbance, high photothermal conversion efficiency and photostability, and exhibited outstanding in vitro PTT effect under NIR laser irradiation. In vivo therapeutic experiments revealed that this CD47-targeted PTT nanoagent, with the assistance of enhanced macrophage phagocytosis, achieved the goal of tumor eradication. Besides, toxicity studies confirmed that Ab-PEG-Bi 2 Se 3 had good biocompatibility. In conclusion, Ab-PEG-Bi 2 Se 3 may serve as an efficient PTT platform in combination with macrophage-mediated immunotherapy to improve antitumor efficacy.
研究领域:
肿瘤学
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纳米技术
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免疫疗法
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Huanhuan Wang,Runze Zhao,Lei Peng,Ao Yu,Yongjian Wang
Atherosclerosis is a primary contributor to cardiovascular disease. Current studies have highlighted the association between the immune system, particularly immune cells, and atherosclerosis, although treatment options and clinical trials remain scarce. Immunotherapy for cardiovascular disease is still in its infancy. Bruton's tyrosine kinase (BTK), widely expressed in various immune cells, represents a promising therapeutic target for atherosclerosis by modulating the anti-inflammatory function of immune cells. This study introduces a polydopamine-based nanocarrier system to deliver the BTK inhibitor, ibrutinib, to atherosclerotic plaques with an active targeting property via an anti-CD47 antibody. Leveraging polydopamine's pH-sensitive reversible disassembly, the system offers responsive, controlled release within the pathologic microenvironment. This allows precise and efficient ibrutinib delivery, concurrently inhibiting the activation of the NF-κB pathway in B cells and the NLRP3 inflammasome in macrophages within the plaques. This treatment also modulates both the immune cell microenvironment and inflammatory conditions in atherosclerotic lesions, thereby conveying promising therapeutic effects for atherosclerosis in vivo. This strategy also provides a novel option for atherosclerosis treatment.
研究领域:
心脏病学
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免疫学
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纳米医学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2019
·
IF 8.355
Yingying Zhang,Hongbin Chen,Hanjie Wang,Tiange Wang,Huizhuo Pan,Wanying Ji,Jin Chang
Immunotherapy has become a promising therapy in cancer treatment. Both photothermal therapy (PTT) and genotoxic chemotherapy can trigger immune responses. On this subject, a synergistic cancer immunotherapy nano-system was developed for treating primary and distant tumors. This long-time, synergistic therapeutic system consisted of two parts: one was indocyanine green (ICG) and sepantronium bromide (YM155) co-loaded mesoporous silica nanoparticles (MSNs) for PTT and genotoxic chemotherapy, which could effectively destroy primary tumors and thus cause exposure of tumor antigens for cancer immunotherapy. The other was silica nanoparticles (nSiO 2 ) coated with magnetic nanoparticles (MNP) and conjugated with anti-CD47 antibody (anti-CD47), which demonstrated a strong antitumor immune effect of distant tumors after PTT and genotoxic chemotherapy. In vitro and vivo results proved that this synergistic system could efficiently inhibit primary and distant tumor growth. We expected that this paper may develop a promising strategy to prevent tumor growth for basic and clinical research.
研究领域:
癌症治疗
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纳米技术
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免疫学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）