JOURNAL OF CONTROLLED RELEASE
·
2022
·
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
·
免疫学
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DOI
PubMed
高影响因子
Cancer Cell International
·
2026
·
IF 7
Siyi Liu,Lin Liang,Zihua Zhou,Chenyu Zhang,Shan Liao,Qian He,Yan Lei,Juan Xu,Gengqiu Luo,Yanling Li,Yanhong Zhou
As a cell surface glycoprotein, CD90 plays a significant role in the initiation and progression of malignancies such as gastric cancer (GC) by influencing tumor cell proliferation, migration, and angiogenesis. However, its specific role in immune evasion in GC and its potential therapeutic value have not been fully explored. In this study, we report that CD90 is highly expressed in GC tissues and is positively correlated with macrophage immune infiltration. Furthermore, we demonstrate that CD90 can mediate immune evasion in GC by affecting the phagocytic function of tumor-associated macrophages (TAMs). Mechanistically, CD90 functions as a scaffold protein, inhibiting the interaction between IGF2BP2 and TRIM21. This inhibition stabilizes the expression of the m6A methylation reader protein IGF2BP2. Subsequently, IGF2BP2 enhances the mRNA stability of the immune checkpoint molecule CD47 in an m6A-dependent manner, leading to the activation of the CD47/SIRPα axis. Ultimately, by inhibiting the phagocytic function of TAMs, CD90 mediates immune evasion in GC. In summary, our work highlights the critical role of the CD90-IGF2BP2-CD47 axis in immune evasion in GC. This finding is expected to provide significant experimental evidence for elucidating the pathogenesis of GC and discovering potential molecular targets for clinical treatment.
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DOI
PubMed
高影响因子
ACS Nano
·
2026
·
IF 17.3
Jinqiao Zhang,Ting Tong,Chang Cai,Xianzhou Cai,Bicheng Sun,Kexin Wen,Xinran Qu,Qin Fan,Ziliang Dong
Radiotherapy, while effective in tumor treatment, often induces upregulation of CD47 checkpoint expression on malignant cells, activating the CD47-SIRPα “don’t eat me” signaling axis to inhibit macrophage-mediated phagocytosis, thereby promoting immune evasion and ultimately compromising therapeutic efficacy. Herein, a radiosensitizer-loaded biomimetic nanodecoy (p@MVs-Sirpα) is constructed by harnessing genetically engineered macrophage-derived vesicles to enhance tumor radioimmunotherapy. p@MVs-Sirpα displays the high surface expression of signal regulatory protein α (SIRPα), enabling it to selectively bind to CD47, a “don’t eat me” signal overexpressed on tumor cells post radiotherapy, thereby competitively blocking the CD47/SIRPα immune checkpoint and promoting macrophage-mediated phagocytosis. Additionally, the nanodecoy is loaded with the radiosensitizing agent polyoxometalates (POMs), which further enhance the efficacy of radiotherapy by modulating the tumor immune microenvironment. This dual-function strategy not only facilitates the immune clearance of tumor cells but also potentiates radiotherapy-induced antitumor responses. p@MVs-Sirpα effectively inhibits the progression of established tumors in multiple murine models. Moreover, in tumor rechallenge experiments, robust and durable immune memory was observed, indicating long-term protection against tumor relapse. Collectively, this study provides a promising proof-of-concept for employing genetically engineered vesicle-based nanodecoy to disrupt radiation-induced immune escape and augment the therapeutic outcomes of radioimmunotherapy.
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Kaiming Li,Ziming Lin,Ting Wu,Jintong Zhou,Jie Wu,Yupeng Zhou,Huimin Gao,Ya Lin,Xufeng Chen,Huae Xu,Xiaolin Li
Small cell lung cancer (SCLC) is a highly lethal malignancy with a < 7 % 5-year survival rate. Platinum-based chemotherapy remains the standard treatment; however, its clinical efficacy is limited. There is an urgent need for new therapeutic strategies. In this study, we developed a RGD labeled liposome (CS/RGD-Lipo) encapsulating both cisplatin and surufatinib as a target delivery system against SCLC, aimed at enhancing ferroptosis to improve cisplatin efficacy, inhibiting angiogenesis, and reversing TAM phenotypes to overcome immunosuppression. Additionally, we combined CS/RGD-Lipo with αCD47 to further enhance antitumor activity. In tumor-bearing mice, CS/RGD-Lipo effectively targeted tumor tissues for the delivery of cisplatin and surufatinib. The combination of CS/RGD-Lipo with αCD47 significantly promoted ferroptosis in SCLC, improved anti-angiogenesis, induced the conversion of M2 macrophages to M1 macrophages, and enhanced the M1 macrophages-mediated antitumor immune response, resulting in a marked inhibition of tumor growth in SCLC mouse models. Taken together, this work demonstrates a feasible therapeutic approach to inhibit SCLC by combining cisplatin, surufatinib, and αCD47 to leverage tumor ferroptosis, angiogenesis inhibition and tumor-associated macrophage polarization.
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2026
·
IF 13.6
Yingtao Zhong,Keyan Zhang,Xinyu Li,Zhuofeng Li,Xinjia Huang,Ziwen Qiu,Junmei Nie,Jiaqi Wang,Shiying Li,Hong Cheng
Despite its critical role in treating localized breast cancer, radiotherapy (RT) rarely provokes systemic immune responses or abscopal effects. In this work, immunological profiling reveals that RT upregulates CD47 and PD-L1 expressions in tumor cells and promotes the accumulation of M2-type tumor-associated macrophages (TAMs), suggesting a potential immunosuppressive mechanism that restricts abscopal responses. To overcome this limitation, a legumain-activated radio-immunological synergist (LARIS) is rationally designed to amplify RT-induced abscopal effects through dual CD47/PD-L1 blockade and TAM repolarization. LARIS is constructed from a bispecific immune checkpoint blockade chimeric peptide (BiCCP) linking CD47-and PD-L1-blocking peptides via a legumain-cleavable linker, and co-formulated with the Toll-like receptor 7/8 agonist R848. Within the tumor microenvironment, abundant legumain can cleave LARIS to release R848 together with the checkpoint blockade peptides, thereby reprogramming TAMs toward an M1 phenotype and mitigating CD47/PD-L1-mediated immune evasion. Both in vitro and in vivo studies demonstrated that LARIS significantly enhances systemic antitumor immunity and effectively induces abscopal responses of RT, thus suppressing the growth of distant and rechallenged tumors. Overall, this work offers a promising strategy to counteract RT-induced immunosuppression and potentiate abscopal effects for improved breast cancer therapy.
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DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 7
·3147
·
IF 4.6
Rui Chang,Xiaohong Chu,Jibing Zhang,Rongrong Fu,Changshun Feng,Dianlong Jia,Rui Wang,Hui Yan,Guangyong Li,Jun Li
Antitumor immunity is an essential component of cancer therapy and is primarily mediated by the innate immune response, which plays a critical role in initiating and shaping the adaptive immune response. Emerging evidence has identified innate immune checkpoints and pattern recognition receptors, such as CD47 and Toll-like receptor 7 (TLR7), as promising therapeutic targets for cancer treatment. Based on the fusion protein Fc-CV1, which comprises a high-affinity SIRPα variant (CV1), and the Fc fragment of the human IgG1 antibody, we exploited a preparation which coupled Fc-CV1 to imiquimod (TLR7 agonist)-loaded liposomes (CILPs) to actively target CT26. WT syngeneic colon tumor models. In vitro studies revealed that CILPs exhibited superior sustained release properties and cell uptake efficiency compared to free imiquimod. In vivo assays proved that CILPs exhibited more efficient accumulation in tumors, and a more significant tumor suppression effect than the control groups. This immunotherapy preparation possessed the advantages of low doses and low toxicity. These results demonstrated that a combination of immune checkpoint blockade (ICB) therapy and innate immunity agonists, such as the Fc-CV1 and imiquimod-loaded liposome preparation utilized in this study, could represent a highly effective strategy for tumor therapy.Keywords:imiquimod;liposome;Fc-CV1;immunotherapy;colon cancer
研究领域:
肿瘤学
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免疫学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2022
·
IF 6.14
Xue-Hui Shi,Jing-Ping Yuan,Ying-Ying Dai,Xing Liu,Shu-Lin Liu,Zhi-Gang Wang
In breast cancer (BC), the tumor microenvironment contains various cell types and extracellular components, of which CD68 and CD47 are two key factors. Recent studies have shown that simultaneous high expression of CD68 and CD47 is associated with poor prognosis in BC. However, there is no direct methodological evidence to support this finding. Here, using our own preparation of different functionalized quantum dots, we successfully achieved dual-color in situ fluorescence imaging of CD68 and CD47 with high spatial resolution. This imaging approach provided directly observable evidence that cancer cells evading immune responses are surrounded by more macrophages, suggesting that the coevolution of CD68 and CD47 during BC development can promote cancer cell metastasis. Taken together, our results provide direct evidence for evaluating prognostic factors of BC and will contribute to our understanding of the tumor microenvironment and its role in tumor evolution.
研究领域:
癌症生物学
·
免疫学
·
分子生物学
·
医学影像
✓ 已验证
DOI
高影响因子
Advanced Science
·
2025
·
IF 14.1
Long-Bo Yu,Peng Wang,Qing-Hua Shen,Qi-Xin Guan,Zhi-Yuan Li,Ying-Ying Han,Xin-Yi Zhang,Qing-Yuan Hu,Cai-Ping Tan
Photosensitizers engineered for spatiotemporal modulation of cluster of differentiation 47 (CD47) in hypoxic tumor microenvironments (TMEs) disrupt immunosuppressive circuits. Herein, we develop two Ir(III) complexes ( Ir1 and Ir2 ) that function as photodynamic therapy (PDT) agents via Type-I/II mechanisms, overcoming hypoxic constraints. Under 630 nm irradiation, Ir1 -mediated PDT ROS-dependently downregulates CD47, enabling spatial control that circumvents hematotoxicity. Concurrently, Ir1 -mediated PDT triggers immunogenic cell death (ICD) via ferroptosis-necroptosis synergy and blocks the CD47-SIRPα immune checkpoint, while promoting M1-polarization of tumor-associated macrophages. In 4T1 murine breast cancer models, Ir1 -PDT achieves potent tumor suppression and transforms immunologically “cold” tumors into “hot” lesions through the synergistic interplay of ICD and CD47 pathway disruption. Collectively, this work establishes a photodynamic CD47-signaling platform for precise immune modulation, offering a clinically translatable alternative to conventional CD47-targeting therapies.
研究领域:
肿瘤学
·
光动力疗法
·
免疫治疗
·
无机化学
·
分子医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Interdisciplinary Medicine
·
2026
·
IF 13.6
Albert Yu,Yibo Hou,Kaibin Huang,Xucan Gao,Rong Zeng,Chaowei Zhu,Chunhui Sun,Guocai Wang,Lei Ye,Shaohua Ma,Tian Meng,Bing Guo,Yubo Zhang,Xiaoyong Dai
For colorectal cancer (CRC), treatment outcomes and prognosis remain poor even when using first-line chemotherapeutics and immunotherapeutics. The main reasons include (i) lack of tumor specificity, severe off-target cytotoxicity leading to adverse side effects, and occurrence of chemoresistance, and (ii) the immunosuppressive “cold” tumor microenvironment (TME). Herein, we demonstrate an example of highly efficient targeted CRC chemoimmunotherapy with cisplatin (CDDP)-containing nanomedicine (CDDP@MSN-Anti-CD47) in a patient-derived organoids xenograft model. The CDDP@MSN-Anti-CD47 is composed of CDDP-loaded mesoporous silica nanoparticles with superficially functionalized anti-CD47 antibodies to target cluster of differentiation CD47, a transmembrane integrin-associated protein that is over-expressed in CRC cells and can bind with signal regulatory protein α on tumor-associated macrophages (TAMs) to maintain the immunosuppressive TME. Our results demonstrated that CDDP@MSN-Anti-CD47 achieved targeted delivery of CDDP to CRC cells with extended release, and induced reactive oxygen species overproduction to inhibit CRC cells and CRC patient-derived organoids growth via activating caspase-3-related apoptosis and immunogenic cell death. DAMPs released following CDDP@MSN-Anti-CD47 treatment promoted the polarization of TAMs from immunosuppressive M2 to pro-inflammatory M1 phenotype and also synergized with the functionalized anti-CD47 antibodies to restore macrophage phagocytic activity against CRC cells. In both CRC cell and patient-derived organoid xenograft models, CDDP@MSN-Anti-CD47 could specifically target the tumor, showing strong anti-tumor effects, prolonged survival rate, and low systemic cytotoxicity. Overall, CDDP@MSN-Anti augments combination chemotherapy and immunotherapy, and can be developed as a novel and promising strategy for the clinical treatment of CRC.
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DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Jing Wang,Nuli Xie,Shan Lu,Bo Xiao,Yangqin Ou,Qingnian Li,Dexian Liu,Wenhu Zhou
Intracerebral hemorrhage (ICH) presents a formidable challenge due to its high mortality and disability rates, primarily attributed to cerebral hematoma formation and ensuing neuroinflammation. Swift hematoma removal is paramount for prognosis, yet existing interventions carry risks and limitations. Notably, elevated CD47 expression on hematoma-associated RBC triggers a “don't eat me” signal, impeding hematoma clearance, while microglial/macrophage erythrophagocytosis exacerbates oxidative stress and the RBC lysate evokes neuroinflammation. To address this conundrum, a multifunctional nanomedicine (TD-CFR), employing DNA tetrahedra (TD) as a carrier for ICH treatment is introduced. The investigations reveal that CpG enhances the phagocytosis of CD47-expressing RBC by microglia/macrophages via lipid metabolism modulation. Integration of CpG into TD preserves its pro-phagocytic efficacy, while TD's double-stranded region enables efficient encapsulation of Rutin, a potent anti-inflammatory and antioxidant flavonoid. Capitalizing on disrupted blood-brain barrier integrity at the hemorrhage site, TD-CFR achieves robust enrichment within cerebral hematoma post-intravenous administration, augmented by folate receptor-mediated targeting of microglia/macrophages. Efficacy assessments in mouse and rabbit ICH models confirm TD-CFR's therapeutic benefits, including hematoma clearance, neuroinflammation suppression, and brain function restoration. Leveraging TD's high biosafety profile and dual active ingredient loading capacity, the study unveils a promising drug treatment paradigm for ICH.
研究领域:
神经科学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Pei Wang,Bohui Zhou,Ziye Liu,Yining Zhao,Robert Chunhua Zhao,Jinhui Peng,Juan Zhang
The accurate detection of immune checkpoint molecules on the surface of tumor cells is of great significance for immunotherapy. Herein, we propose a method based on cellular interface supported cascade signal amplification mediated by CRISPR/Cas13a system for in situ analysis of immune checkpoint molecules on bladder cancer cells. CD47 and EpCAM on bladder cancer cells can be sensitively monitored through T7 transcription amplification, CRISPR/Cas13a system and HCR triple signal amplification. Moreover, the established method can specifically differentiate EpCAM and CD47 positive bladder cancer cells and well serve for the evaluation of two kinds of membrane protein inhibitors. In a word, the method we proposed can successfully realize in situ analysis of immune checkpoint molecules on bladder cancer cells for guiding immunotherapy.
研究领域:
癌症生物学
·
分子生物学
·
免疫学
·
生物技术
✓ 已验证
产品关联
DOI
高影响因子
Nano Today
·
2021
·
IF 20.722
Meng Lin,Zhenzhen Yang,Yiliang Yang,Yiwei Peng,Jiajia Li,Yitian Du,Qi Sun,Datong Gao,Quan Yuan,Yu Zhou,Xinyi Chen,Xianrong Qi
Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment and promote the tumor progression via multiple mechanisms. CD47 is overexpressed in most malignant tumors and acts as a “don’t eat me” signal to inhibit phagocytosis . We utilized CRISPR/Cas9 technology to knock out CD47 to guarantee the long-lasting anti-tumor immune responses. However, the reprogrammed TAMs are vulnerable to the inhibitory cytokines and tend to be transformed back into TAMs, and CD47 blockade alone may not be sufficient to elicit effective immune responses. We combined CD47 blockade with an immune-activating cytokine IL-12 for synergistic anti-tumor efficacy by genetically engineering the tumor cells into factories of IL-12 to in situ reprogram TAMs. Firstly, we designed a selective responsiveness accelerated gene delivery system named HPT-PFs that was dual modified with hyaluronic acid (HA) and tumor microenvironment sensitive peptides (TMSP) to simultaneously deliver plasmids for CD47 knockout and IL-12 production. Due to tumor-specific transfection and excellent endosome escape ability of HPT-PFs vector, more than 27% of tumor cells lost CD47 expression after HPT-PFs mediated gene editing, thus eliciting the phagocytosis by macrophages. And higher than 500 ng/ml of IL-12 was produced by tumor cells after HPT-PFs mediated pIL-12 expression, indicating the successful engineering of tumor cells into factories of IL-12. In melanoma-bearing mice models, drastic elevation of M1-polarized TAMs and secretion of inflammatory cytokines were observed when combined CD47 knockout with IL-12 production, which led to significant inhibition of tumor growth. Our study suggested that combination of CRISPR-mediated CD47 blockade with IL-12 production in tumor cells could synergistically promote macrophage-mediated immunotherapy, paving the way for CRISPR-based in situ engineering tumor cells for effective immunotherapy.
研究领域:
癌症生物学
·
免疫学
·
基因治疗
·
生物技术
✓ 已验证
产品关联
DOI
高影响因子
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