JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2025
·
IF 14.3
Chenqian Feng,Susu Xiao,Min Mu,Xiaoxiao Wang,Wei Yu,Shulin Pan,Hui Li,Rangrang Fan,Bo Han,Gang Guo
Colorectal peritoneal carcinomatosis (CRPC) is a manifestation of colorectal cancer characterized by aggressive tumor growth. Clinically, patients are typically treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. However, this strategy is only suitable for a subset of patients and may result in severe side effects. Therefore, we explored a novel approach using green-engineered materials that we developed an injectable hydrogel (CPE) based on polyphenol-borate ester bonds by functionalizing chitosan. These biopolymer composites exhibit excellent biocompatibility, mitigating drug-related toxicities. Our hydrogel delivery system concurrently administers cabazitaxel and imiquimod (R837) for localized chemotherapy and immunotherapy. Cabazitaxel-mediated chemotherapy induces immunogenic cell death (ICD) of tumor cells, releasing tumor-associated antigens (TAAs), that promote dendritic cell maturation and cytotoxic T lymphocyte (CTL) infiltration. The in situ release of the TLR7 agonist R837 further stimulates the immune system, inducing an effective and sustained antitumor immune response tailored to CRPC. In summary, by establishing an in situ drug reservoir, we effectively inhibited tumor invasion and progression and induced a durable immune response, offering a new perspective on localized immunotherapy for the clinical treatment of CRPC.
研究领域:
肿瘤学
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生物材料科学
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Tongyi Shang,Xinying Yu,Yuan Gu,Rong Du,Yanjun Cai,Yuwei Li,Guodong Zheng,Chaoqun Wang,Jian Zhang,Jifang Liu,Shisong Han,Bin Yang
Cancer immunotherapy is the most promising method for tumor therapy in recent years, among which the macrophages play a critical role in the antitumor immune response. However, tumor-associated macrophages (TAMs) usually display the tumor-promoting M2 phenotype rather than the tumor-killing M1 phenotype. Moreover, the over-expressed CD47 on tumor cells severely hinders the function of macrophages by blocking the CD47/SIRPα pathway. Herein, a nano-assembly system of CHTR/siRNA was constructed through the host-guest interaction of a hyperbranched amino-functionalized β-cyclodextrin and immune agonist imiquimod (R848), while CD47 siRNA was loaded inside through electrostatic interaction. The Toll-like receptor (TLR) 7/8 agonist R848 can “re-educate” macrophages from the protumoral M2 phenotype to antitumoral M1 phenotype, while CD47 siRNA can down-regulate the “don't eat me” CD47 signal on the surface of cancer cells and enhance the phagocytosis of cancer cells by macrophages. Through the dual regulation of TAMs, the immunosuppressive tumor microenvironment was relieved, and the host-guest drug-carrying system resulted in synergistic immunotherapy effect on tumors and inhibited tumor growth. The facile self-assembly of nanodrug offers a new strategy in co-delivery of multiple therapeutic agents for cascade cancer immunotherapy.
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
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Bo Chen,Ruijie Huang,Wei Zeng,Wei Wang,Yuanzeng Min
The immunosuppressive tumor microenvironment (TME) greatly limits the actual outcome of immunotherapy. Therefore, it is urgent to develop appropriate strategies to reshape the TME and ultimately induce a strong immune response. Here, we developed a dual-functional liposome loaded with the photothermal agent IR808 near the infrared region (NIR) and Toll-like-receptor-7 (TLR7) agonist loxoribine prodrug (Lipo@IR808@Loxo) to achieve NIR light-triggered photothermal therapy (PTT) and the targeted delivery of immune adjuvants. Under NIR irradiation, Lipo@IR808@Loxo could greatly improve the efficiency of PTT to directly kill tumor cells and release tumor-associated antigens, which could work together with loaded loxoribine to relieve the immunosuppressive TME, effectively promoting the activation of antigen-presenting cells and subsequent antigen presentation . In this way, Lipo@IR808@Loxo could act as an in situ therapeutic cancer vaccine, eventually inducing a potent antitumor T-cell response. When further combined with immune checkpoint blockade, Lipo@IR808@Loxo-mediated photothermal immunotherapy could not only eliminate the primary tumors but also inhibit the growth of distant tumors, thus enhancing the abscopal effect.
研究领域:
肿瘤学
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免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Xitong Ren,Haochen Yao,Jiali Sun,Fuxin Xue,Linjie Cui,Yajun Xu,Kazuo Sakurai,Na Shen,Zhaohui Tang
Immune checkpoint blockade (ICB) therapy represents a promising approach widely embraced for its sustained efficacy upon activation of the body’s immune responses. Nonetheless, its effectiveness exhibits significant variability among patients, with a response rate below 30 %. A key limitation is the insufficient tumor infiltration and specific priming of CD8 + T cells. To address this, we develop ROS-responsive TLR7/8 nanoagonists {methoxy poly(ethylene glycol)- b -poly-[(N-2-hydroxyethyl)-aspartamide]- g -thioketal-R848}, designated as R848 NPs, wherein the C-4 amino of R848 is chemically blocked to enable selective release under endogenous tumor ROS conditions, thereby mitigating the severe systemic cytokine storms associated with R848. Additionally, ultrasound (US) is employed to induce immune cell death and facilitate intratumoral enrichment of R848 NPs. The proposed combination treatment, R848 NPs+US, effectively enhances antigen presentation by dendritic cells (DCs), facilitates intratumoral distribution of active R848, mitigates systemic inflammatory responses, promotes the release of damage-associated molecular patterns, and upregulates the expression of costimulatory molecules on DCs. Ultimately, R848 NPs+US plays a crucial role in bolstering CD8 + T cells immunity, synergizing with αPDL1 for CT26 tumor suppression (rate: 99.0 %, Q value: 1.68), eliciting memory immunity, and preventing tumor rechallenge. This work provides a novel strategy to potentiate the cancer immunity and a guidance for ICB therapy.
研究领域:
癌症免疫疗法
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纳米技术
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免疫学
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肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Polymers
·
2022
·Vol. 14
·期 24
·5466
·
IF 4.967
Changcai Teng,Xiongyan Meng,Yeqin Hu,Hongzhao Mao,Huiting Li,Jing Yang,Tiantian Sun,Shuai Meng,Chengli Zong
Small synthetic TLR7/8-agonists can be used as vaccine adjuvants to enhance cell and humoral-mediated immune responses to specific antigens. Despite their potency, after local injection they can be dispersed to undesired body parts causing high reactogenicity, limiting their clinical applications. Here we describe a vaccination strategy that employs the covalent conjugate of a mannose and TLR7/8 agonist as a vaccine adjuvant to take advantage of mannose binding C-type lectins on dendritic cells to enhance the vaccine’s immunogenicity. The mannose-TLR7/8 agonist conjugate can self-assemble into nanoparticles with the hydrophilic mannose on the outside and hydrophobic TLR7/8 agonist inside. Although its ability to stimulate HEK-BlueTMhTLR7/8 cells dropped, it can efficiently stimulate mouse bone marrow-derived dendritic cells as indicated by the up-regulation of CD80 and CD86, and higher cytokine expression levels of TNF-α, IL6, and IL-12p70 than the native TLR7/8 agonist. In vivo, vaccination using the SARS-CoV-2 RBD trimer as the antigen and the conjugate as the adjuvant induced a significantly higher amount of IgG2a. These results suggest that the mannose-TLR7/8-agonist conjugate can be used as an effective vaccine adjuvant.Keywords:adjuvants;mannose;TLR7/8 agonist;immune responses;cytokines;antibody
研究领域:
免疫学
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病毒学
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药学
✓ 已验证
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-9
·
IF 5.228
Gao Ningning,Zhong Jingjing,Wang Xiaodong,Jin Zhenchao,Li Wang,Liu Yu,Diao Yuwen,Wang Zhulin,Jiang Wenqi,Jin Guangyi
As new treatment approaches, both immunotherapy and targeted treatments have been used in the clinical treatment of cancers. These therapies are different from traditional surgery, chemotherapy and radiotherapy. Use of a combination of immunotherapy and targeted treatments may improve tumor clearance. We investigated the feasibility of combining tyrosine kinase inhibitors (TKIs, targeted drugs) and SZU-101 (a novel TLR7 agonist synthesized by our laboratory). Thirteen different TKIs were combined with or without SZU-101 and studied to determine their effects on immunocytes. On the basis of the distinctive results, lapatinib and sunitinib were selected for further tumor-inhibition investigation and determination of the underlying mechanism. Interestingly, we found lapatinib to work better with SZU-101, enhancing tumor clearance in vivo , without affecting the TLR7-NF-κB pathway activated by the TLR7 agonist in mouse spleen lymphocytes and bone marrow dendritic cells (BMDCs).
研究领域:
肿瘤学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ORGANIC & BIOMOLECULAR CHEMISTRY
·
2024
·Vol. 22
·期 14
·2764-2773
·
IF 2.9
Yue Song,Wenjie Fan,Chen Yao,Heng Wang,Xiuxiang Lu,Yumin Wang,Pengxiang Liu,Yanjie Ma,Zhen Zhang,Jiang Wang,BeiBei Chu,Lijun Shi,Guoyu Yang,Mengdi Wang
Pattern recognition receptors (PRRs) play a critical role in the innate immune response, and toll-like receptor 7 (TLR7) is an important member of PRRs. Although several TLR7 agonists are available, most of them are being tested clinically, with only one available on the market. Thus, it is imperative to develop new TLR7 agonists. In this study, we designed and synthesized three kinds of quinazoline derivatives and five kinds of pyrrolo[3,2-d]pyrimidine derivatives targeting TLR7. The antiviral efficacy of these compounds was evaluated in vitro and in vivo. Our findings indicated that four kinds of compounds showed exceptional antiviral activity. Furthermore, molecular docking studies confirmed that compound 11 successfully positioned itself in the pocket of the TLR7 guanosine loading site with a binding energy of −4.45 kcal mol−1. These results suggested that these compounds might be potential antiviral agents.
研究领域:
免疫学
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药物化学
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病毒学
✓ 已验证
DOI
高影响因子
Discovery Medicine
·
2024
·Vol. 36
·期 186
·1420-1429
·
IF 2
Shimaa Saad El-Din,Basma Emad Aboulhoda,Amira Hassouna,Marwa M Shakweer,Mansour A Alghamdi,Doha Essam,Mohamed Essam,Nawaf A AlRakaf,Hanaa M Elzahed,Asmaa Selmy,Dina Sabry,Dina M Mekawy
Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently attracted great attention due to their crucial anti-inflammatory and regenerative properties. This work aims to examine the curative impact of intra-articular injection of BM-MSCs-derived exosomes in ameliorating osteoarthritis (OA) progression in rats and to explore the interaction between circular RNA of Yes-associated protein 1 ( circYAP1 ) and microRNA-21 ( miRNA-21 ) in the rat knee joints. Methodology: Gene expression circYAP1 , miRNA-21 , toll-like receptor-7 ( TLR7 ), aggrecan, and collagen type II were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the rat articular tissues. In addition, the Enzyme-linked immunosorbent assay (ELISA) technique was used to estimate the level of the inflammatory markers interleukin 4 (IL-4), interleukin 10 (IL-10), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α); and the oxidative markers glutathione (GSH), malondialdehyde (MDA) and total reactive oxygen species (ROS). Histopathological examination using Hematoxylin and Eosin (H&E) staining of the rat articular tissue was also performed along with an estimation of the articular cartilage thickness. Results: Our results showed that BM-MSCs-derived exosomes significantly elevated circYAP1 gene expression level ( p < 0.05) along with subsequent downregulation of miRNA-21 and TLR7 ( p < 0.05). These effects impacted the inflammatory milieu of rat articular surfaces, where there was a significant reduction ( p < 0.05) of the pro-inflammatory and oxidative markers with significantly increased production of the anti-inflammatory and antioxidative markers ( p < 0.05). Marked elevation in aggrecan and collagen type II gene expression was also found in the treated groups ( p < 0.05). Conclusion: Those data suggest that BM-MSCs-derived exosomes have a crucial role in mitigating OA symptoms and pathology progression and might be regarded as an effective as well as acceptable treatment option for OA.
研究领域:
再生医学
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干细胞生物学
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分子生物学
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骨科
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Chuwen Luo,Chaoying Kong,Yuxiao Zhang,Yajun Xu,Zhaohui Tang
Systemic immunotoxicity caused by off-target activation is still a critical obstacle to clinical translation of imidazoquinoline (IMDQ) drugs, a kind of TLR7/8 agonists. Here, we present an ultrasound-responsive, azide-modified IMDQ nano-prodrug (IMDQ-N3 NPs) that enables spatiotemporally controlled activation through ultrasound, improving the selectivity and safety. Concomitantly, riboflavin-based sonosensitizers were co-delivery to these nanoparticles, increasing their local concentration surrounding the prodrug, achieving a 12.2-fold enhancement in the ultrasonic reduction rate of IMDQ-N3. In murine models, IMDQ-N3 NPs demonstrated no weight loss and negligible systemic inflammatory factor elevation relative to equivalent-dose unmodified IMDQ. Combined with ultrasound irradiation, IMDQ-N3 NPs demonstrated 35.2-fold higher tumor distribution of active drug compared to non-irradiated free IMDQ-N3, achieving 95.7% tumor suppression and 60% long-term survival. Flow cytometry analysis revealed enhanced dendritic cell maturation, cytotoxic T-cell infiltration, and durable immune memory. This work establishes a generalizable platform for precision delivery of immunostimulatory agents, addressing key translational challenges in cancer immunotherapy.
研究领域:
癌症免疫治疗
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纳米医学
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药物递送
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生物工程
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cancer Nanotechnology
·
2023
·Vol. 14
·期 1
·1-18
·
IF 5.7
Lu Dehua,Xu Yanming,Yang Xiaodong,Li Ying,Li Mengqing,Zheng Yuanyuan,Wang Yuenan,Wang Weihu,Wang Shubin,Gao Jing,Liu Yajie
Background Increasing evidence indicates that radiotherapy (RT) has synergistic inhibitory efficiency with immunotherapy agents in multiple cancers and enhances abscopal effects by regulating the innate immune response, which was further investigated in this study. Neutrophils are recruited in radiated tumors. Therefore, neutrophil membrane-coated nanoparticles potentially deliver R837 (Toll-like receptor 7 agonist) to radiated tumors.Methods A novel nanoparticle R837@PLGA@Neu was prepared by initially assembling PLGA (poly (lactic-co-glycolic acid)) with R837 (TLR7 agonist) into R837@PLGA followed by coating with neutrophil membrane. Characterizations of R837@PLGA@Neu were performed. Tumor targeting efficiency was evaluated by in vivo fluorescent imaging of CT26-bearing mice. Treatments of R837@PLGA@Neu combined with RT were carried out in unilateral and bilateral CRC tumor-bearing mice, followed by validations of immune cells in tumors by flow cytometry.Results The characteristics of R837@PLGA@Neu were well identified, and it was confirmed to have high uptake ability and low cytotoxicity in colorectal cancer (CRC) cells in vitro, as well as its strong tumor-targeting efficiency in vivo in CRC tumor-bearing mice. The exciting findings were that R837@PLGA@Neu combined with RT exerted prominent tumor inhibition not only in radiated tumors, but also in distant tumors without RT, suggesting its enhancement of the efficacy and abscopal effect of RT. The possible underlying mechanisms were remodeling of the tumor microenvironment by triggering mature dendritic cells and CD8+ T cells.Conclusion In summary, our findings suggested that neutrophil membrane-derived nanoparticle R837@PLGA@Neu with high uptake ability and low cytotoxicity showed strong tumor-targeting efficiency, and combination with RT had a promising effect in CT26-bearing mice via immune cell regulation. Our results provide a probable combination strategy for CRC treatment.
研究领域:
肿瘤学
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免疫疗法
·
纳米技术
·
放射生物学
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癌症免疫学
✓ 已验证
产品关联
DOI
高影响因子
Nano Research
·
2021
·Vol. 15
·期 1
·510-518
·
IF 8.897
Wu Jia-Si,Li Jia-Xian,Shu Na,Duan Qi-Jia,Tong Qi-Song,Zhang Jing-Yang,Huang Yong-Cong,Yang Si-Yu,Zhao Zhi-Bin,Du Jin-Zhi
Tumor associated macrophages (TAMs) tend to exhibit tumor-promoting M2 phenotype and contribute to the development of immunosuppressive microenvironment of solid tumors. Reprograming TAMs from M2 into tumoricidal M1 phenotype is robust for stimulating tumor immunosuppressive microenvironment (TIME). In this study, we developed a poly(amidoamine) (PAMAM) derivative dendrimer (denoted as fourth generation- N,N -diethylaminoethyl (G4-DEEA)) for efficient loading of Toll-like receptor 7 and 8 (TLR7/8) agonist (R848) to remodel the TIME for potent cancer immunotherapy. G4-DEEA exhibited a high loading capacity of R848 up to 35.9 wt% by taking advantage of its dendritic structure. The resulting formulation (designated as G4-DEEA@R848) effectively polarized M2 macrophages into M1 phenotype in vitro , and improved the maturation and activation of antigen-presenting cells. In the 4T1 orthotopic breast cancer model, G4-DEEA@R848 showed a stronger tumor inhibitory effect than free drug. The mechanistic studies suggested that G4-DEEA@R848 could significantly stimulate the TIME by repolarizing TAMs into M1 phenotype, reducing the presence of immunosuppressive myeloid cells and increasing the infiltration of tumor cytotoxic T cells. This study provides a simple but effective dendrimer-based strategy to improve the formulation of R848 for improved cancer immunotherapy.
研究领域:
癌症免疫治疗
·
药学
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Ying Xu,Jing Yang,Xiongyan Meng,Shuai Meng,Tiantian Sun,Ning Ding,Chengli Zong
Covalently linking an adjuvant to an antigenic protein enhances its immunogenicity by ensuring a synergistic delivery to the immune system, fostering a more robust and targeted immune response. Most adjuvant-protein conjugate vaccines incorporate only one adjuvant due to the difficulties in its synthesis. However, there is a growing interest in developing vaccines with multiple adjuvants designed to elicit a more robust and targeted immune response by engaging different aspects of the immune system for complex diseases where traditional vaccines fall short. Here, we pioneer the synthesis of a dual-adjuvants protein conjugate Vaccine 1 by assembling a toll-like receptor 7/8 (TLR7/8) agonist, an invariant natural killer T cell (iNKT) agonist with a clickable bicyclononyne (BCN). The BCN group can bio-orthogonally react with azide-modified severe acute respiratory syndrome coronavirus-2 receptor-binding domain (SARS-CoV-2 RBD) trimer antigen to give the three-component Vaccine 1 . Notably, with a mere 3 μg antigen, it elicited a balanced subclass of IgG titers and 20-fold more IgG2a than control vaccines, highlighting its potential for enhancing antibody-dependent cellular cytotoxicity. This strategy provides a practicable way to synthesize covalently linked dual immunostimulants. It expands the fully synthetic self-adjuvant protein vaccine that uses a single adjuvant to include two different types of adjuvants.
研究领域:
免疫学
·
病毒学
·
药物化学
·
疫苗研发
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）