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
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 20
·6940-6949
·
IF 6.843
Guiqiang Zhang,Ning Wang,Haifeng Sun,Xiao Fu,Shumei Zhai,Jiwei Cui
Combination cancer immunotherapy that synergizes the advantages of multiple therapeutic agents has shown great potential in tumor treatment. Herein, we report the one-step assembly of therapeutic nanoparticles (NPs) to co-deliver photosensitizers and adjuvants for combination photodynamic therapy (PDT) and immunotherapy. The NPs are obtained via self-assembly of chlorin e6 (Ce6) and imidazoquinoline-based TLR7 agonists (IMDQ), which results in a high loading efficacy of 72.2% and 27.8% for Ce6 and IMDQ, respectively. Upon laser irradiation, the resulting NPs could not only effectively induce photodynamic immunogenic cancer cell death, but also elicit robust antitumor immunity, leading to significant inhibition of both primary and distant tumors in a bilateral tumor model. This study demonstrates the potential of self-assembled NPs in co-delivering multiple therapeutics for potential immunotherapy to enhance the antitumor efficacy.
研究领域:
生物医学工程
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肿瘤免疫学
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纳米医学
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DOI
PubMed
高影响因子
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
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产品关联
DOI
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
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DOI
高影响因子
Theranostics
·
2023
·
IF 12.4
Jiqian Zhang,Shasha Zhu,Mingxu Zhao,Mengni Zhou,Xiaoling Zhu,Xin Qing,Zhilai Yang,Pengfei Wei,Guoying Zhang,Weiling He,Yongqiang Yu,Xuesheng Liu
Rationale: Tumor ablation can cause severe pain to patients, but there is no satisfactory means of analgesia available. In addition, recurrence of residual tumors due to incomplete ablation threatens patient safety. Photothermal therapy (PTT), a promising approach for tumor ablation, also faces the aforementioned problems. Therefore, developing novel photothermal agents that can efficiently relieve PTT-associated pain and potentiate the PTT efficacy are urgently needed. Methods: The Pluronic F127 hydrogel doped with indocyanine green (ICG) was served as photothermal agent for PTT. Mouse model that inoculation of tumor near the sciatic nerve was constructed to assess the PTT-evoked pain. Subcutaneous and sciatic nerve vicinal tumor-bearing mice were used to test the efficacy of PTT. Results: PTT-evoked pain depends on an increase in tumor temperature and is accompanied by the activation of TRPV1. A simple introduction of local anesthetic (LA) ropivacaine into ICG-loaded hydrogels relieves PTT-induced pain and exerts long-lasting analgesia compared with opioid analgesia. More interestingly, ropivacaine upregulates major histocompatibility complex class I (MHC-I) in tumor cells by impairing autophagy. Therefore, a hydrogel co-doped with ropivacaine, TLR7 agonist imiquimod and ICG was rationally designed. In the hydrogel system, imiquimod primes tumor-specific CD8 + T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8 + T cells through upregulating MHC-I. Consequently, the hydrogel maximumly increases CD8 + T cells infiltration into tumor and potentiates PTT efficacy. Conclusion: This study for the first time provides an LA-dopped photothermal agents for painless PTT and innovatively proposes that a LA can be used as an immunomodulator to potentiate the PTT efficacy.
研究领域:
癌症治疗
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生物医学工程
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药学
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免疫学
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产品关联
DOI
PubMed
高影响因子
ACS Infectious Diseases
·
2023
·
IF 5.3
Wenzhu Yin,Bihua Deng,Zeyu Xu,Haiyan Wang,Fang Ma,Mingxu Zhou,Yu Lu,Jinqiu Zhang
Adjuvants are essential for the induction of robust immune responses against vaccine antigens. Small-molecule TLR7 agonists hold high potential for this purpose. In this communication, imiquimod (IMQ) bearing a cholesterol lipid moiety derivative, IMQ-Chol, was designed and synthesized as a vaccine adjuvant, which could release parent IMQ molecules in aqueous conditions via amide bond hydrolysis. We performed a series of immunological evaluations by cooperating with the inactivated foot-and-mouth disease virus (FMDV). All of the results confirmed that IMQ-Chol could stimulate the body for a prolonged time to produce strong humoral and cellular immunity with a balanced Th1/Th2 immune response through a TLR7-related MAPK pathway. In addition, the results of the proof-of-concept vaccine indicated IMQ-Chol had a good effect on preventing and treating FMD in pigs.
研究领域:
免疫学
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病毒学
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药学
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兽医学
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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
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产品关联
DOI
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
·
免疫学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Small
·
2020
·Vol. 16
·期 38
·2003543
·
IF 11.459
Lingqiao Liu,Yi Wang,Xing Guo,Jingya Zhao,Shaobing Zhou
The progress of antitumor immunotherapy is usually limited by tumor-associated macrophages (TAMs) that account for the highest proportion of immunosuppressive cells in the tumor microenvironment, and the TAMs can also be reversed by modulating the M2-like phenotype. Herein, a biomimetic polymer magnetic nanocarrier is developed with selectively targeting and polarizing TAMs for potentiating immunotherapy of breast cancer. This nanocarrier PLGA-ION-R837 @ M (PIR @ M) is achieved, first, by the fabrication of magnetic polymer nanoparticles (NPs) encapsulating Fe 3 O 4 NPs and Toll-like receptor 7 (TLR7) agonist imiquimod (R837) and, second, by the coating of the lipopolysaccharide (LPS)- treated macrophage membranes on the surface of the NPs for targeting TAMs. The intracellular uptake of the PIR @ M can greatly polarize TAMs from M2 to antitumor M1 phenotype with the synergy of Fe 3 O 4 NPs and R837. The relevant mechanism of the polarization is deeply studied through analyzing the mRNA expression of the signaling pathways. Different from previous reports, the polarization is ascribed to the fact that Fe 3 O 4 NPs mainly activate the IRF5 signaling pathway via iron ions instead of the reactive oxygen species-induced NF-κB signaling pathway. The anticancer effect can be effectively enhanced through potentiating immunotherapy by the polarization of the TAMs in the combination of Fe 3 O 4 NPs and R837.
研究领域:
纳米技术
·
癌症免疫学
·
生物医学工程
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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