JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Zhengjie Meng,Xue Fang,Bowen Fu,Cheng Qian,Zheng Yang,Yunhao Bai,Xinyue Tao,Haixiao Huang,Chenyu Ma,Wenjun Miao,Hao Ren,Aiyun Wang,Xueming Li
Melanoma is a malignant skin cancer that is prone to metastasis in the early stage and has a poor prognosis. Immunomodulatory therapy for melanoma has been a hot research topic in recent years. However, low immune cell infiltration and loss of tumor immunogenicity may occur in tumors, resulting in low response rates to immunotherapy . Thus, immunomodulatory therapy is usually used in combination with chemotherapy and radiotherapy. Development of combined therapeutic strategies with low systemic toxicity, high immune responsiveness and long-term inhibition of metastasis and recurrence of melanoma is the goal of current research. In this study, the insoluble immune adjuvant imiquimod (R837) was prepared as nanocrystals and coated with polydopamine (PDA) to form R837@PDA, which was then loaded into chitosan hydrogel (CGP) to form the drug-loaded gel system, R837@PDA@CGP (RPC), to combine immunomodulation effects, induction of immunogenic cell death (ICD) effects and immune-enhancement effects. After treatment with RPC, ICD in melanoma was induced, and the infiltration rate of cytotoxic T cells (CTLs) in melanoma was also significantly enhanced, which turned the tumor itself into an in situ vaccine and boosted the cancer-immunity cycle at the tumor site. Therefore, melanoma growth, metastasis and recurrence were notably inhibited.
研究领域:
肿瘤学
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免疫学
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纳米技术
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Shichao Zhang,Yijiang Liu,Yuhan Xie,Chenchun Ding,Renjie Zuo,Zhenzhen Guo,Shiyong Qi,Tingting Fu,Weibin Chen
Breast cancer represents a substantial contributor to mortality rates among women with cancer. Chemical dynamic therapy is a promising anticancer strategy that utilizes the Fenton reaction to transform naturally occurring hydrogen peroxide (H2O2) into hydroxyl radicals (•OH). Additionally, cancer immunotherapy using immune drugs, such as imiquimod (R837), has shown promise in activating T cells to kill tumor cells. In this study, we proposed a Fe3O4@R837 smart nanoplatform that can trigger the Fenton reaction and induce immune responses in breast cancer treatment. Furthermore, we performed transcriptome sequencing on breast cancer samples and used the R package (limma) to analyze differential expression profiles and select differentially expressed genes (DEGs). We obtained clinical information and RNA expression matrix data from The Cancer Genome Atlas database to perform survival analysis and identify prognostic-related genes (PRGs) and molecular subtypes with distinct prognoses. We used the TIMER 2.0 web and other methods to determine the tumor immune microenvironment and immune status of different prognostic subtypes. We identified DPGs by taking the intersection of DEGs and PRGs and performed functional analyses, including gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, to elucidate potential mechanisms. Subsequently, we constructed a protein–protein interaction network using the STRING database to visualize the interactions between the DPGs. We screened hub genes from the DPGs using the Cytoscape plugin and identified six hub genes: CD3E, GZMK, CD27, SH2D1A, ZAP70, and TIGIT. Our results indicate that these six key genes regulate immune cell recruitment to increase T-cell cytotoxicity and kill tumors. Targeting these key genes can enhance immunotherapy and improve the breast cancer prognosis.
研究领域:
癌症生物学
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分子生物学
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免疫学
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生物信息学
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基因组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2020
·Vol. 41
·期 5
·724-735
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IF 2.997
Zhaocheng Li,Jiyuan Gao,Zexing Xiang,Honglei Zhang,Yibei Wang,Xuefei Zhang
Cancer immunotherapy is a promising method for cancer therapy. Imiquimod (R837) is a molecule that could activate immune systems for cancer immunotherapy, but an easily manufactured biocompatible carrier to deliver R837 may be needed to overcome the disadvantages of R837. Micelles formed by biocompatible copolymers have been widely used to deliver chemotherapeutic drugs but not immunotherapeutic drugs. In this study, R837 was linked to an amphiphilic biodegradable copolymer mPEG-b-PLA via acid-sensitive Schiff bases. The molecular structures were investigated by 1 H nuclear magnetic resonance, gel permeation chromatography and Fourier transform infrared spectroscopy. The product could be self-assembled into micelles with R837 content as high as 22.4%. Owing to acid-cleavable Schiff bases, the release of R837 from micelles was markedly accelerated under acidic media. Consequently, the micelles linked with R837 stimulated the expression of major histocompatibility complex II-stimulating molecules on the surface of RAW 264.7 macrophages at pH 6.5 but not pH 7.4. By using human umbilical vein endothelial cells as the in vitro model, it was shown that the polymer carriers and R837-linked micelles were minimally cytotoxic and did not induce the activation of endothelial cells under physiological pH, which suggested the relatively high biocompatibility. In conclusion, this study successfully developed pH-responsive immunotherapeutic drug-loaded micelles that could activate macrophages at acidic pH in vitro. The high biocompatibility of the micelles to endothelial cells also indicated the potential uses under in vivo conditions.
研究领域:
药剂学
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免疫学
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聚合物化学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Yuting Cao,Yan Zhou,Jinbin Pan,Xinyu Zhong,Jianmin Ding,Xiang Jing,Shao-Kai Sun
The minimal invasive percutaneous microwave ablation (MWA) combined with immunotherapy is a promising technique in clinic for the treatment of primary and metastatic tumors. However, elaborate encapsulation carrier designs, complex cellular engineering, and poor applicability are the vexing problems difficult to solve currently. Herein, a general strategy was proposed for the design of an injectable microwave-sensitive immune hydrogel for combined MWA and immunotherapy in vivo for the first time. The mix-and-use hydrogel composed Food and Drug Administration (FDA)-approved components were fabricated by introducing various immunostimulants regardless of hydrophilicity and hydrophobicity into the alginate (ALG)-Ca 2+ hydrogel. As a proof of concept, an immunoadjuvant (R837) was employed to synthesize the R837-ALG-hydrogel for systematic studies. This immune hydrogel owns ultra-facile synthesis process, good microwave-sensitivity, adjuvant encapsulation efficiency of nearly 100%, good biocompatibility and syringeability, and large-scale production capability, which could be easily injected into the primary tumor for enhancing MWA. Moreover, the loaded R837 could motivate in situ vaccination by making the utmost of the tumor-associated antigens released after MWA, thereby inducing the robust tumor-specific antitumor immunity to suppress the distant metastatic tumor in vivo. The proposed injectable microwave-sensitive immune hydrogel paves a facile but general avenue with great clinical translation potential for the minimal invasive personalized oncotherapy.
研究领域:
肿瘤学
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生物医学工程
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2023
·
IF 6.6
Yukun Wang,Wenjing Li,Bi Lin,Ying Yuan,Pengbo Ning,Xiaofeng Tao,Ruichan Lv
Photothermal therapy has a remarkable effect on the destruction of tumors. It kills tumor cells by photothermal ablation and induces immunogenic cell death by activating the immune response in tumor tissues. However, inhibition of the tumor immune microenvironment suppresses PTT-induced body-specific anti-tumor immunity. In this study, we designed the GdOF@PDA-HA-R837-hydrogel complex to achieve NIR-II imaging-guided photothermal ablation and enhanced immune response. Due to the doping of Yb and Er elements and the presence of a polydopamine coating, the synthesized nanoparticles enable NIR-II and photoacoustic imaging of tumor tissues, which will help in the integration of multimodal tumor imaging for diagnosis and treatment. Polydopamine is used as a photothermal agent and drug carrier because of its excellent photothermal ability and high drug loading capacity under 808 nm near infrared light. Hyaluronic acid can bind to specific receptors on the surface of cancer cells, allowing nanoparticles to aggregate around the tumor, thus enhancing the targeting ability of nanoparticles. In addition, imiquimod (R837) has been used as an immune response modulator to enhance the immunotherapeutic effect. The presence of a hydrogel enhanced the retention effect of nanoparticles in the tumor. We demonstrate that the combination of photothermal therapy with immune adjuvants effectively induces ICD, which in turn stimulates the activation of specific anti-tumor immunity and enhances the effect of photothermal therapy in vivo.
研究领域:
肿瘤学
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生物医学工程
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纳米医学
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免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 26
·6147-6158
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IF 7
Xiaoxi Song,Chun Zhang,Mengyuan Xing,Chunyan He,Dongxu Wang,Lijuan Chong,Xiuli Zhang,Minghui Chen,Jingjing Li
Photothermal therapy (PTT) is an effective and well-documented approach to thermally ablate tumors. However, the side effect of distal metastasis and recurrence limit its further expansion. At the same time as PTT was developed, the employment of imaging to monitor the treatment of tumors also became meaningful. Herein, as a proof of concept, gadolinium-doped mesoporous carbon nanoparticles (Gd-MCNs) were prepared as nanocarriers, MRI contrast agents, and PTT agents by a one-step hard template method, which realized Gd doping and carbon filling simultaneously, while retaining enough pore space for drug loading. After loading the immune adjuvant, R837, and the coating of tumor extracellular vesicle, the obtained biomimetic nanoparticles (EV@Gd-MCNs-R837) not only allowed tumor MRI, but also inhibited the primary tumor and its metastasis with long-term immune memory in vivo. This study provides proof for the potential of Gd-MCNs-based biomimetic nanoparticles for targeted PTT/immune-enhanced synergistic theranostic of tumors.
研究领域:
纳米技术
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生物医学工程
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癌症治疗
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分子影像
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免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 14
·2805-2813
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IF 5.344
Shiyu Wan,Boya Zhang,Sai Li,Bin He,Yuji Pu
Photoimmunotherapy, which combines local photothermal therapy (PTT) with immunological stimulation, is a promising modality for cancer treatment. Herein, we have reported a photothermal-immunotherapy of melanoma using pegylated black phosphorus nanosheets (BP-PEG NSs) and imiquimod (R837) as the photothermal conversion agent and the immunoadjuvant, respectively. The photothermal stability of BP NSs was remarkably enhanced after the modification of poly(ethylene glycol) (PEG) by electrostatic interactions. The in situ generation of tumor-associated antigens by PTT elicited a strong immune response in the presence of R837, achieving a photoimmunotherapy of B16 melanoma. This photoimmunotherapy stimulated a stronger immune response both in vitro and in vivo than monotherapy, inducing a much greater release of cytokines such as IL-6, IL-12, and TNF-α. In vivo antitumor studies in B16 tumor-bearing mice demonstrated that photoimmunotherapy showed the best tumor inhibition effects. Our study suggested that BP-PEG NS-based PTT primed with an immunoadjuvant can be used for synergistic photoimmunotherapy of melanomas.
研究领域:
癌症治疗
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纳米技术
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免疫学
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材料科学
✓ 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
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纳米技术
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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
BIOMATERIALS
·
2023
·
IF 14
Mo Chen,Huangjuan Li,Jing Zang,Yueyang Deng,Hongjun Li,Qing Wu,Tianyuan Ci,Zhen Gu
Cancer vaccine holds vast promise in potentiating tumor immunotherapy. Here, we developed a simple cancer vaccine based on the liquid nitrogen-treated cells (LNT cells) that engineered by one-shot shocking of the live tumor cells in liquid nitrogen . In this vaccine, the obtained LNT cells served as both tumor antigens and delivery vehicles to load the adjuvant imiquimod (R837). This design could achieve efficient co-uptake of antigen/adjuvant by antigen presenting cells (APCs) and prolong in vivo retention of tumor antigens and adjuvants. This adjuvant-loaded LNT cells augmented in vivo antitumor responses and enhanced survival in melanoma-bearing mouse model compared with conventional whole-cell vaccine of the mixture of tumor lysis and adjuvant.
研究领域:
肿瘤学
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免疫治疗
·
癌症研究
✓ 已验证
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
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癌症免疫学
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生物医学工程
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY OF MATERIALS
·
2021
·
IF 9.811
Jiexin Li,He Ren,Yaping Sun,Gengqi Liu,Xingyue Yang,Qian Qiu,Yuanmeng Ding,Jonathan F. Lovell,Yumiao Zhang
Cancer peptide vaccines face challenges for antigen delivery and presentation. In the present work, we develop a self-assembled magnetic micelle delivery system for CD8+ T-cell epitopes that produces strong cellular immune responses. Hydrophobically modified imiquimod R837 and Zn1.15Fe1.85O4 are coencapsulated in the core of Pluronic F127 block copolymer micelles. Magnetic Zn1.15Fe1.85O4 enables externally targeted delivery and enrichment of micelles in lymph nodes. Furthermore, metal ions are found to enhance vaccine immunogenicity. F127 micelles were chemically modified by a self-immolative linker so that antigens are rapidly and reversibly grafted on micelles in an aqueous solution. With the assistance of an external magnetic field, once the magnetic micelles are delivered to lymph nodes and taken up by immune cells, intracellular glutathione cleaves the disulfide bond and releases pristine short peptide antigen. Delivery to lymph nodes is tracked by magnetic resonance and fluorescence imaging. The use of this vaccine system eradicated tumors in a murine tumor model. Thus, integrating multiple functionalities in a single micellar delivery system, including responsive linkage, multiple immunostimulatory molecules, targeted delivery, and bimodal imaging, demonstrates the potential for theranostic approaches to develop a new generation of cancer vaccines.
研究领域:
癌症研究
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免疫学
·
纳米技术
·
生物医学工程
·
治疗诊断学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Haoyu Chen,Xiaoying Kong,Jiahui Yan,Tianyi Wang,Yaqian Lv,Fenglang Zhang,Danping Liu,Yingshan Qu,Jun Fu,Wei Han,Jinsheng Shi
Combined dynamic tumor therapy of photodynamic therapy (PDT), sonodynamic therapy (SDT) and microwave dynamic therapy (MDT) can overcome the limitations of single reactive oxygen species (ROS)-based therapy (including limited tissue penetration depth and low ROS production). However, changes in the tumor microenvironment caused by ROS amplification and oxygen depletion induce severe immunosuppression at the tumor site, indicating effective immunosensitization of the tumors are urgently needed. Here, melanin-hematoporphyrin-chloroquine R837-hyaluronic acid (MHRH) nanoplatform that can simultaneously respond to 980 nm laser /1064 nm laser/ultrasonic/microwave was prepared for PDT/SDT/MDT, achieving outbreak of ROS in deep tumor. More importantly, the photothermal ablation and the participation of chloroquine R837 of MHRH NPs reversed the immunosuppression caused by oxygen depletion after ROS outbreak by promoting DCs maturation and secretion of macrophage exosomes. In summary, the natural MHRH nano-platform supplies an obvious anti-tumor “butterfly effect” through ROS outbreak, thermal ablation and significant immunosuppressive reversal, which provides a new and promising combined strategy of ROS-dynamic therapy and immune agonists in deep tumor tissues.
研究领域:
癌症治疗
·
纳米技术
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免疫治疗
·
生物医学工程
·
肿瘤学
✓ 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）