BIOMACROMOLECULES
·
2025
·
IF 5.4
Min Mu,Hui Li,Susu Xiao,Chenqian Feng,Bo Chen,Rangrang Fan,Nianyong Chen,Gang Guo
Triple-negative breast cancer is an aggressive subtype of breast cancer characterized by rapid disease progression and a high risk of metastasis. The advent of immunotherapy has revolutionized the treatment paradigm for breast cancer. Herein, a manganese-based nanoagonist (FA-IR780/EGCG@MnO2) featuring mitochondrial targeting and photothermal therapy (PTT) was constructed for STING activation and photothermal metalloimmunotherapy. The engineered FA-IR780/EGCG@MnO2 was constructed to enable the generation of mitochondria-targeted reactive oxygen species under laser irradiation to release mitochondrial DNA (mtDNA) and induce immunogenic cell death. The released mtDNA, as an endogenous danger-associated molecular pattern, could activate the STING pathway. Concurrently, Mn2+ further enhanced the activation of the STING pathway. By combining the synergistically enhanced the activation of the STING pathway, the engineered nanoagonist facilitated the DC maturation and T lymphocyte infiltration, resulting in long-term immune memory to inhibit tumor growth. This study revealed the potential combination of metalloimmunotherapy and PTT for rational regulation of the immune microenvironment.
研究领域:
肿瘤学
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免疫学
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生物材料
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Shuang Liang,Haiyan Ma,Yue Liu,Linna Hai,Yiwei Tian,Yangyang Sun,Zhaohui Wang
The initiation of tumor-specific T cell responses is critically dependent on antigen-presenting cells (APCs). Nevertheless, as the most dominant APCs in tumors, M2-like macrophages largely restrained T cell activation due to inefficient antigen cross-presentation. Herein, we rationally designed a nano-immunomodulator (FANP) to restore the antigen presentation capability of M2-like macrophages by amplifying stimulator of interferon genes (STING) activation. FANPs were fabricated by self-assembly of Fe 3+ and Raddeanin A (RA), which rapidly degraded when reaching tumor microenvironment. The released Fe 3+ induced the polarization of M2-like macrophages into M1 phenotype, followed by RA stimulation for amplified STING activation, allowing robust antigen cross-presentation and T cell-driven anti-tumor response, leading to effective tumor regression in both immunogenic and poor-immunogenic tumor models. Notably, FANPs exhibited intensive STING activation in human tumor samples, showing potential for clinical impact. Our work offers a simple and robust strategy to re-educate M2-like macrophages by augmenting STING activation for 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
Science Advances
·
2024
·Vol. 10
·期 38
·
IF 11.7
Jianing Li,Tianze Wu,Weidong Wang,Yimin Gong,Mingzhu Lu,Mengmeng Zhang,Wanyue Lu,Yaming Zhou,Yannan Yang
In situ vaccine (ISV) is a versatile and personalized local immunotherapeutic strategy. However, the compromised viability and function of dendritic cells (DCs) in a tumor microenvironment (TME) largely limit the therapeutic efficacy. We designed a hybrid nanoparticle–based ISV, which accomplished superior cancer immunotherapy via simultaneously scavenging reactive oxygen species (ROS) and activating the stimulator of interferon genes (STING) pathway in DCs. This ISV was constructed by encapsulating a chemodrug, SN38, into diselenide bond–bridged organosilica nanoparticles, followed by coating with a Mn2+-based metal phenolic network. We show that this ISV can activate the STING pathway through Mn2+ and SN38 comediated signaling and simultaneously scavenge preexisting H2O2 in the TME and Mn2+-catalyzed •OH by leveraging the antioxidant property of diselenide and polyphenol. This ISV effectively activated DCs and protected them from oxidative damage, leading to remarkable downstream T cell activation and systemic antitumor immunity. This work highlights a nanoparticle design that manipulates DCs in the TME for improving the ISV.
研究领域:
癌症免疫治疗
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纳米技术
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免疫学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Yeyang Wu,Yanmei Li,Ni Yan,Jiaqi Huang,Xinyu Li,Keyan Zhang,Zhenming Lu,Ziwen Qiu,Hong Cheng
Stimulator of the interferon genes (STING) pathway is appealing but challenging to potentiate the innate anti-tumor immunity. In this work, nuclear-targeted chimeric peptide nanorods (designated as PFPD) are constructed to amplify innate immunity through localized DNA damage and STING activation. Among which, the chimeric peptide (PpIX-FFVLKPKKKRKV) is fabricated with photosensitizer and nucleus targeting peptide sequence, which can self-assemble into nanorods and load STING agonist of DMXAA. The uniform nanosize distribution and good stability of PFPD improve the sequential targeting delivery of drugs towards tumor cells and nuclei. Under light irradiation, PFPD produce a large amount of reactive oxygen species (ROS) to destroy nuclear DNA in situ , and the released cytosolic DNA fragment will efficiently activate innate anti-tumor immunity in combination with STING agonist. In vitro and in vivo results indicate the superior ability of PFPD to activate natural killer cells and T cells, thus efficiently eradicating lung metastatic tumor without inducing unwanted side effects. This work provides a sophisticated strategy for localized activation of innate immunity for systemic tumor treatment, which may inspire the rational design of nanomedicine for tumor precision therapy.
研究领域:
癌症治疗
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纳米技术
·
免疫学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Fei Wang,Shuhan Chen,Yinhe Xia,Caihong Liu,Zhou Xu,Ruilong Song,Wenfeng Liu,Tingting Liu,Gang Chen,Qingquan Liu
Influenza epidemics remain a global public health challenge. Vaccination with nucleic acid-based vaccines, which trigger strong cellular and humoral immune responses, represents a promising approach for preventing virus infection. However, its effectiveness relies on efficient delivery and an immunoadjuvant. Here, we constructed a gene- and nanoengineered vaccine delivery platform via modifying MnO2 nanoparticles (NPs) onto the surface of the M13 phage, which carried the hemagglutinin stem gene of influenza A virus preceded by a eukaryotic initial transcriptional region. Specifically, the M13 phage protected the inserted nucleic acid vaccine against degradation due to the existence of capsid proteins. MnO2 NPs released Mn2+ ions under the acidic condition of endolysosomes, thereby promoting the cytoplasmic delivery of phage vaccines, which significantly improved the antigen expression. Moreover, Mn2+ acted as a potent adjuvant for dendritic cell maturation by activating the cGAS/STING pathway. Immunization with the engineered phage vaccine induced CD4+ T cell, CD8+ T cell, and humoral immune responses in mice. In infected mouse models, the vaccines ameliorated weight loss, survival rate, lung virus titers, and pulmonary pathologies and conferred full protection against influenza viruses. Collectively, we developed a dual-engineered phage vaccine platform, offering an alternative regimen for optimizing nucleic acid vaccines, which may have broad applications in the rational design of vaccine formulations.
研究领域:
病毒学
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免疫学
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药学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Yechun Jiang,Weinan Zhang,Litao Liu,Yayun Wu,Weiqi Li,Jun Liang,Hui Shen,Shu Fang,Xianyu Huang,Zhaoyou Chu,Lingling Xu,Haisheng Qian
The immunosuppressive niche of the breast cancer microenvironment and the vascular basement membrane significantly hinder the efficacy of nanoparticle-based antitumor immunotherapy delivered via the vascular system. This study describes the design of a puncture-delivered tumor implant, utilizing a photo-cross-linked gelatin methacryloyl hydrogel as the matrix, loaded with Cu0.5Mn2.5O4 nanoparticles (CMO NPs) and monomethyl fumarate (MMF), enabling the sustained release of nanoparticles through matrix metalloproteinase-responsive degradation. Mechanistically, CMO NPs induce cuproptosis and immunogenic cell death (ICD) in tumor cells, while synergizing with MMF to trigger substantial mtDNA release into the cytosol. Subsequently, the liberated mtDNA synergizes with Mn2+ to activate the cGAS-STING signaling pathway, which cooperates with ICD to enhance CD8+ T cell infiltration and increase the levels of related inflammatory factors in the breast tumor microenvironment. Notably, the implant significantly enhances the efficacy of αPD-1 therapy by modulating PD-L1/PD-1 expression. In summary, the implant designed in this study provides a practical strategy for nanoparticle delivery and immunotherapy of breast cancer.
研究领域:
生物材料
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纳米医学
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免疫学
·
肿瘤学
·
药物递送
·
生物工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Chengjie Huang,Xiao Zhi,Tianbao Ye,Xiuyuan Wang,Ke Li,Yiyang Li,Qiang Zhang,Lai Jiang,Xianting Ding
Vaccination is essential for preventing and controlling infectious diseases, along with reducing mortality. Developing safe and versatile adjuvants to enhance humoral and cellular immune responses to vaccines remains a key challenge in vaccine development. Here, we designed hierarchical mesoporous MOF-801 (HM801) using a Cocamidopropyl betaine (CAPB) and a Pluronics F127 in an aqueous phase system. Meanwhile, we synthesized a novel SARS-CoV-2 nanovaccine (R@M@HM801) with a high loading capacity for both the STING agonist (MSA-2) and the Delta receptor binding domain (Delta-RBD) antigen. R@M@HM801 enhanced MSA-2 and RBD utilization and effectively co-delivered MSA-2 and RBD antigens to antigen-presenting cells in the draining lymph nodes, thereby promoting the activation of both T and B cells. Lymphocyte single-cell analysis showed that R@M@HM801 stimulated robust CD11b + CD4 + T cells, CXCR5 + CD4 + T follicular helper (T fh ), and durable CD4 + CD44 + CD62L − , CD8 + CD44 + CD62L − effector memory T cell (T EM ) immune responses, and promoted the proliferative activation of CD26 + B cells in vivo. Meanwhile, R@M@HM801 induced stronger specific antibodies and neutralization of pseudovirus against Delta compared to the RBD + MAS-2 and RBD + MAS-2 + Alum vaccines. Our study demonstrated the efficacy of a hierarchical mesoporous HM801 and its potential immune activation mechanism in enhancing adaptive immune responses against viruses and other diseases.
研究领域:
免疫学
·
病毒学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2024
·
IF 4.8
Li-Li Zhang,Jia-Ying Xu,Wei Wei,Zhi-Qiang Hu,Yan Zhou,Jia-Yang Zheng,Yu Sha,Lin Zhao,Jing Yang,Qi Sun,Li-Qiang Qin
Background Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy, limiting the clinical application of this treatment. Evidence shows the potential benefits of dietary restriction in improving metabolic profiles and age-related diseases. The present study investigated the effects and mechanisms of dietary restriction in radiation-induced intestinal injury. Methods The mice were randomly divided into the control group, 10 Gy total abdominal irradiation (TAI) group, and groups pretreated with 30% caloric restriction (CR) for 7 days or 24h fasting before TAI. After radiation, the mice were returned to ad libitum. The mice were sacrificed 3.5 days after radiation, and tissue samples were collected. Results CR and fasting reduced radiation-induced intestinal damage and promoted intestinal recovery by restoring the shortened colon length, improving the impaired intestinal structure and permeability, and remodeling gut microbial structure. CR and fasting also significantly reduced mitochondrial damage and DNA damage, which in turn reduced activation of the cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) pathway and the production of type I interferon and other chemokines in the jejunum. Since the cGAS/STING pathway is linked with innate immunity, we further showed that CR and fasting induced polarization to immunosuppressive M2 macrophage, decreased CD8 + cytotoxic T lymphocytes, and downregulated proinflammatory factors in the jejunum. Conclusions Our findings indicated that CR and fasting alleviate radiation-induced intestinal damage by reducing cGAS/STING-mediated harmful immune responses.
研究领域:
放射生物学
·
免疫学
·
胃肠病学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
Dongdong Xu,Jun Hu,Jiawei Mei,Jun Zhou,Zhengxi Wang,Xudong Zhang,Quan Liu,Zheng Su,Wanbo Zhu,Hongjian Liu,Chen Zhu
Repetitive implant-related infections (IRIs) are devastating complications in orthopedic surgery, threatening implant survival and even the life of the host. Biofilms conceal bacterial-associated antigens (BAAs) and result in a "cold tumor"-like immune silent microenvironment, allowing the persistence of IRIs. To address this challenge, an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum (CFCP) was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response. Specifically, enhanced sonodynamic therapy (SDT) from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA (dsDNA). Immunogenic dsDNA promoted dendritic cell (DC) maturation through activation of the stimulator of interferon gene (STING) and amplified the immune stimulation of neutrophils via interferon-β (IFN-β). At the same time, enhanced BAA presentation aroused humoral immunity in B and T cells, creating long-term resistance to repetitive infections. Encouragingly, CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention.
研究领域:
骨科手术
·
免疫学
·
纳米技术
·
传染病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2022
·
IF 18.962
Hao Tian,Guohao Wang,Wei Sang,Lisi Xie,Zhan Zhang,Wenxi Li,Jie Yan,Ye Tian,Jie Li,Bei Li,Yunlu Dai
Dendritic cells (DCs) play a key role in the presentation of tumor antigens to initiate innate and adaptive immune responses. While the tumor microenvironment (TME) contains a network of immunosuppressive factors that inhibit the differentiation and maturation of DCs. Immunoadjuvants have been focusing on modulating DCs function to improve cancer immunotherapy . Herein, a phenolic nanoadjuvant was developed by self-assembly of the sonosensitizer polymer (PEG-b-IR), GSH inhibitor (sabutoclax), Mn 2+ and TME acidic sensitive phenolic polymer (PEG-b-Pho) via metal–phenolic coordination. The combinational action of SDT-mediated ICD effect and Mn 2+ promoted the activation of the cGAS-STING pathway significantly enhanced DCs maturation. Furthermore, this phenolic nanoadjuvant greatly sensitizes tumors to PD-L1 checkpoint blockade immunotherapy, resulting in efficiently inhibiting the growth of distant tumors and restraining lung metastasis. Therefore, our work provides the potential to remedy the therapeutic limitation of insufficient antitumor immunity for enhanced cancer immunotherapy.
研究领域:
癌症研究
·
免疫学
·
纳米技术
·
治疗学
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Zhicheng Le,Jiang Qian,Haolin Chen,Zepeng He,Runcheng Tan,Hong Liu,Zhenfu Wen,Yi Shi,Zhijia Liu,Yongming Chen
Encouraging results from clinical trials have underscored the potential of gene-pulsed dendritic cell (DC) vaccines as a viable approach for immunotherapy. However, insufficient gene delivery and functional deficiencies in antigen presentation, migratory capacity and cytokine release of DC vaccines limited its broader clinical application. Here, a combinatorial design of cationic gemini amphiphile (GA) molecular library based on the four-component Ugi reaction (Ugi-4CR) has been developed to identify versatile non-viral vectors for gene-engineered DC vaccines. We demonstrated that the leading GA enabled robust transfection of plasmid DNA or mRNA into the DCs through the formation of minimalist binary complexes, which exhibited great advantages of low carrier/gene ratios, high gene loading efficiency and well biocompatibility. The identified GA stimulated strong type I interferon (IFN) expression via the intracellular stimulator of interferon genes (STING) pathway and enhanced DC maturation and activation, which could potentially facilitate strong immunogenicity of DC vaccines. Importantly, DC maturation and activation could be further strengthened by co-delivering maturation stimuli with mRNA/GA complexes, and adoptive transfer of gene-engineered DC vaccines elicited strong T cell responses and thus inhibited tumor growth in vivo . The further studies indicated GAs can be formulated into lipid nanoparticle (LNP)-like quinary complexes that presented 6.9-fold higher mRNA delivery efficiency on the DCs than the commercial Lipofectamine 2000. These results suggest that GA-based molecular library is a powerful platform to develop versatile gene delivery vectors for immune cell engineering.
研究领域:
免疫学
·
分子生物学
·
药学
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
Fundamental Research
·
2023
·
IF 6.2
Liping Liu,Jiayu Zhao,Zichao Huang,Yudi Xu,Hongyu Chen,Ruirui Qiao,Wantong Song,Zhaohui Tang,Thomas P. Davis,Xuesi Chen
ABSTRACT In recent years, the use of nanotechnologies to improve immunotherapy efficiency has attracted increasing interest in preventive and therapeutic cancer vaccine design. However, current nanocarriers are restricted by difficulties in the systematic spatial coordinative transport of antigens, which greatly hampers the immune response efficacy of nanovaccines. Herein, we designed a mannan-decorated stimulator of the interferon genes (STING)-activating vaccine carrier for spatial coordinative stimulation of antigen-specific immune responses and elicitation of robust antitumor immunity. Mannan-decoration as the shell could significantly enhance the lymph node draining ability of the nanovaccines, especially in CD8 + dendritic cells (DCs). Azole molecule end-capped polylactic acid-polyethylenimine (PLA-PEI-4BImi) with innate stimulating activity was applied as the inner core for coordinating antigen-presenting cell (APC) activation and antigen cross-presentation. In the in vivo therapy study, single usage of this nanovaccine could achieve a 93% tumor suppression rate in the B16-OVA tumor model, which is superior to the commercialized aluminum adjuvant. This study demonstrates that a rational design of vaccine carriers for solving spatial transmission issues could greatly improve cancer vaccine efficiencies.
研究领域:
纳米技术
·
免疫学
·
癌症研究
·
生物医学工程
·
药学
✓ 已验证
DOI
PubMed
高影响因子
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