Matter
·
2023
·
IF 18.9
Zhiqin Cao,Lanfang Ren,Le Niu,Rui Zhao,Nanhui Liu,Qi Zhuang,Feng Pan,Zhuang Liu,Yiyun Cheng,Yang Yang,Qian Chen
Summary Cancer vaccines have attracted tremendous interest in the field of cancer immunotherapy due to their ability to trigger tumor-specific immune responses to destroy cancer cells. Herein, we demonstrate that dendrimers coordinated with manganese ions (GT-Mn 2+ ) could self-assemble with peptides to form a cancer vaccine, which could be internalized by dendritic cells (DCs) via specific macropinocytosis-dependent and lipid-raft-related pathways and then dissociated gradually to release peptides to achieve efficient antigen cross-presentation and stimulate the cGAS-STING pathway. Additionally, GT-Mn 2+ could package multiple neoantigens to form an effective “personalized” cancer vaccine and has exhibited excellent therapeutic effects when used in combination with anti-PD-L1. Thus, our work presents an innovative peptide carrier to construct an effective “personalized” cancer vaccine that shows great promise to achieve effective cancer immunotherapy for different patients in clinic.
研究领域:
癌症免疫疗法
·
纳米医学
·
疫苗学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Lei Cao,Huixiang Tian,Man Fang,Zhe Xu,Dongsheng Tang,Juan Chen,Jiye Yin,Haihua Xiao,Kun Shang,Hongbin Han,Xiangping Li
cGAS-STING pathway, as an essential intracellular immune response pathway, has attracted much attention in tumor immunotherapy. However, low metabolic stability of conventional STING agonists limits their clinical application. Recent study shows that chemotherapeutic drugs cisplatin and camptothecin (CPT) can activate cGAS-STING pathway and induce immune response by DNA damage. Nevertheless, the ability of chemotherapeutic drugs to activate STING is so weak that new strategies are required to improve drug delivery efficiency for enhanced DNA damage, and then efficiently activate cGAS-STING pathway. Herein, we have developed a hybrid platinum prodrug (CPT-Pt (IV)) which can be triggered to release cisplatin and CPT in tumor cells. CPT-Pt (IV) with high hydrophobicity is further self-assembled with a ROS sensitive polymer (P1) and mPEG 2k -DSPE into ROS responsive nanoparticles (NPs). NPs could accumulate in the tumor site to release cisplatin and CPT, resulting in DNA double damage and finally activating cGAS-STING pathway, inducing DC cells maturation and increasing tumor infiltration of CD8 + T cells on colorectal cancer mouse model. This study showed that common DNA targeted drugs can activate the cGAS-STING pathway in situ via nano delivery system, and enhance the effect of chemotherapy and immunotherapy, which provide a new strategy for clinical antitumor therapy.
研究领域:
肿瘤学
·
药学
·
免疫学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Zishan Zeng,Yue Sun,Jingwen Jiang,Xiaoyu Xu,Huanxin Lin,Wanzhen Li,Dong Zheng,Yanjuan Huang,Chunshun Zhao
Gastric cancer constitutes a malignant neoplasm characterized by heightened invasiveness, posing significant global health threat. Inspired by the analysis that gastric cancer patients with Helicobacter pylori ( H. pylori ) infection have higher overall survival, whether H. pylori can be used as therapeutics agent and oral drug delivery system for gastric cancer. Hence, we constructed engineered H. pylori for gastric cancer treatment. A type Ⅱ H. pylori with low pathogenicity, were conjugated with photosensitizer to develop the engineered living bacteria NIR-triggered system (Hp-Ce6). Hp-Ce6 could maintain activity in stomach acid, quickly infiltrate through mucus layer and finally migrate to tumor region owing to the cell morphology and urease of H. pylori . H. pylori, accumulated in the tumor site, severed as vaccine to activate cGAS-STING pathway, and synergistically remodel the macrophages phenotype. Upon irradiation within stomach, Hp-Ce6 directly destroyed tumor cells via photodynamic effect inherited by Ce6, companied by inducing immunogenic tumor cell death. Additionally, Hp-Ce6 exhibited excellent biosafety with fecal elimination and minimal blood absorption. This work explores the feasibility and availability of H. pylori -based oral delivery platforms for gastric tumor and further provides enlightening strategy to utilize H. pylori invariably presented in the stomach as in-situ immunomodulator to enhance antitumor efficacy.
研究领域:
肿瘤学
·
药学
·
免疫学
·
生物技术
✓ 已验证
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2022
·
IF 10.334
Xiaohua Xie,Xiaofeng Wu,Dongsheng Zhao,Ying Liu,Qiyue Du,Yitian Li,Yaping Xu,Yuhang Li,Yan Qiu,Yungang Yang
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with high mortality and limited effective therapy. Herein, we reported that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), used in depression and anxiety treatment, also exhibited therapeutic activities in IPF. Fluvoxamine inhibited cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), restrained the activation of their downstream targets, including PERK/ eIF2α/ c-Myc/ miR-9–5p/ TBPL1 and TBK1/ YAP/ JNK1/2/ Bnip3/ CaMKII/ cofilin signaling, thus attenuated the activation and migration of fibroblasts upon TGF-β1 challenge. Fluvoxamine dose-dependently improved pulmonary function, decreased the expression of inflammatory factors, reduced excessive production of extracellular matrix, and thus alleviated bleomycin (BLM)-induced lung fibrosis in mice. Moreover, fluvoxamine at a dose of 10 mg/ kg showed similar efficacy as pirfenidone (PFD) at a dose of 30 mg/kg in a mice model of lung fibrosis. In summary, our results suggest that fluvoxamine is an effective anti-fibrotic agent for IPF.
研究领域:
药理学
·
肺科学
·
免疫学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Shengnan Huang,Chenyang Zhou,Chengzhi Song,Xiali Zhu,Mingsan Miao,Chunming Li,Shaofeng Duan,Yurong Hu
Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO 2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn 2+ and produce O 2 , resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn 2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.
研究领域:
肿瘤学
·
生物材料学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Zheng Jia,Xinyao Zhou,Jingjing Liu,Xinqi De,Yifan Li,Zaixing Yang,Haoyuan Duan,Fang Wang,Junwei Ge
The use of biomimetic mineralization strategy is promising to solve the problem of poor stability and immune effect of subunit antigens. However, non-specifically inducing protein mineralization is still a challenge. we hypothesized that rhamnolipids with both protein and metal binding capacity could be used to develop more functional and biocompatible calcium mineralized nanoparticle (RMCP). The results show that rhamnolipids synergistically enhanced the mineralization of protein with manganese ions and improved 21 % the loading antigens of RMCP compared to manganese calcium phosphate nanoparticles. Transmission electron microscopy (TEM) and Dynamic Light Scattering (DLS) showed particle size of RMCP is 260 ± 12.1 nm with spherical morphology. In vitro experiments have shown that RMCP effectively activate immune cells through the cGAS-STING and NLRP3 pathways and demonstrated a higher level of cytokines in RAW264.7 Macrophages. In vivo, RMCP triggered an increased IgG titer with 16.5-fold IgG2a/IgG1 ratio compared to the aluminum adjuvant which improved the recovery status after challenge in mice. We used biological surfactants for the first time to enhance the biomimetic mineralization process of subunit antigen, which provides a new approach for constructing calcium-based biocompatible antigen delivery vectors, helping to develop a new generation of stable, efficient, and safe subunit vaccines.
研究领域:
免疫学
·
纳米技术
·
疫苗开发
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Shuai Liu,Xintao Gao,Yulan Yin,Jing Wang,Kehong Dong,Dayong Shi,Xiaochen Wu,Chuanlong Guo
Silk fibroin (SF) has excellent biocompatibility and biodegradability as a biomaterial. The purity and molecular weight distribution of silk fibroin peptide (SFP) make it more suitable for medical application. In this study, SFP nanofibers (molecular weight ∼30kD) were prepared through CaCl 2 /H 2 O/C 2 H 5 OH solution decomposition and dialysis, and adsorbed naringenin (NGN) to obtain SFP/NGN NFs. In vitro results showed that SFP/NGN NFs increased the antioxidant activity of NGN and protected HK-2 cells from cisplatin-induced damage. In vivo results also showed that SFP/NGN NFs protected mice from cisplatin-induced acute kidney injury (AKI). The mechanism results showed that cisplatin induced mitochondrial damage, as well as increased mitophagy and mtDNA release, which activated the cGAS-STING pathway and induced the expression of inflammatory factors such as IL-6 and TNF-α. Interestingly, SFP/NGN NFs further activated mitophagy and inhibited mtDNA release and cGAS-STING pathway. Demonstrated that mitophagy-mtDNA-cGAS-STING signal axis was involved in the kidney protection mechanism of SFP/NGN NFs. In conclusion, our study confirmed that SFP/NGN NFs are candidates for protection of cisplatin-induced AKI, which is worthy of further study.
研究领域:
生物材料
·
药理学
·
肾病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aggregate
·
2024
·
IF 13.9
Aihui Wang,Liqun Li,Liqian Zheng,Bang-Ping Jiang,Yihao Liu,Rimei Huang,Huimin Qiu,Shichen Ji,Hong Liang,Xing-Can Shen
Antibacterial lysozyme hydrogels show attractive advantages in wound dressings due to their intrinsic antibacterial activity and excellent biochemical and mechanical properties. Unfortunately, the development of such hydrogels is still greatly limited due to the lack of universal gelation strategies. Herein, a universal gelation strategy between lysozyme-nanofiber (LZF) and inorganic salts is proposed for the first time to construct functional nanofibrous lysozyme-based hydrogels. In particular, divalent anions are found to universally drive LZF for the aggregation and transformation into three-dimensional nanofibrous network hydrogels via electrostatic interaction, and the key role of divalent anions in the gelation is further proved by molecular dynamics simulation. In addition, near-infrared light-mediated photothermal characteristics are endowed with LZF to enhance its inhibitory activity of multidrug-resistant bacteria by the skeleton modification with genipin to produce genipin-conjuagted LZF (GLZF). As a distinct application paradigm, the brilliant immunomemory MnSO 4 -crosslinked GLZF hydrogel is constructed to sensitize the cGAS-STING pathway and skillfully establish an antibacterial immune microenvironment. It can excellently realize the anti-recurrence of diabetic wound infection via photo-enhanced bacterial killing and the cGAS-STING pathway. Thereby, it paves the way to employ the universal divalent anion-mediated gelation strategy for the future development of functional inorganic salt hybrid lysozyme hydrogels.
研究领域:
材料科学
·
生物材料
·
生物医学工程
·
免疫学
·
伤口愈合
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Xiaowen Hou,Chunlin Ren,Xiaodong Zeng,Yukun Hu,Yicheng Zhao,Yuxin Cheng,Qiusi Luo,Taotao Ding,Xue Qiao,Yuqin Liao,Guo-Bo Li,Bengui Ye,Xuechuan Hong,Yuling Xiao
DNA-targeting chemotherapies can activate the stimulator of interferon genes (STING) pathway but elicit limited immune responses. We engineered 3P-SN38 , a long-circulating nanoplatform enabling sustained, tumor-targeted SN38 delivery and NIR-II imaging. To further potentiate immune activation and minimize STING agonist toxicity, SR717 was co-encapsulated, forming 3P-SN38@SR717 . 3P-SN38@SR717 induced immunogenic cell death and dendritic cell maturation in vitro , with combination therapy showing superior effects. In vivo , 3P-SN38@SR717 effectively activated the cGAS-STING pathway, enhancing anti-tumor immunity. Significant increases in the populations of CD8 + T cells, mature dendritic cells, and M1-type macrophages were observed, along with elevated levels of cytokines, including IL-6 and TNF-α. This integrated nanoplatform offers a promising approach for chemoimmunotherapy, enabling durable tumor control with reduced dosing and improved safety.
研究领域:
纳米医学
·
免疫治疗
·
肿瘤学
·
药学
·
生物医学成像
✓ 已验证
DOI
PubMed
高影响因子
Colloid and Interface Science Communications
·
2025
·
IF 4.7
Shouguang Wang,Xiaofei Zhang,Dunmin Zhuang,Lina Dong,Bo Li
Objective Breast cancer remains a global health challenge due to limitations of conventional therapies, such as drug resistance and systemic toxicity. This study aimed to develop a novel synergistic chemo-immunotherapy platform by constructing Mn 2+ -coordinated oxidized hyaluronic acid (OHA)-based nanoparticles co-loaded with phloretin (PHL) (OHA@Lys/PHL Mn 2+ ). Methods A nanosystem was engineered using oxidized hyaluronic acid (OHA) modified with lysine (Lys) to co-encapsulate PHL and Mn 2+ ions. The anti-tumor efficacy was evaluated in vitro (4 T-1 breast cancer cells) and in vivo (4 T-1 tumor-bearing mice), including assessments of proliferation inhibition, apoptosis induction, reactive oxygen species (ROS) accumulation, DNA damage, cGAS-STING pathway activation, and dendritic cell (DC) maturation. Combination therapy with cisplatin (CDDP) was also investigated. Results OHA@Lys/PHL Mn 2+ achieved 80.3 % cell viability inhibition on 4 T-1 cells. Combined with CDDP, it further suppressed proliferation, induced apoptosis, and enhanced ROS accumulation. Mechanistically, the nanosystem induced DNA double-strand damage and activated the cGAS-STING pathway. In vivo , OHA@Lys/PHL Mn 2+ monotherapy showed significant tumor inhibition (46.4 %, p < 0.001). Combination with CDDP achieved near-complete tumor suppression (86.7 % inhibition) and reduced lung metastasis. The in vivo mechanism results indicated that nanosystem triggered DNA damage, activated cGAS-STING signaling, and significantly promoted DC maturation (48.5 % vs. 28.2 % in controls). Conclusion This strategy offers a promising and clinically translatable approach for advanced breast cancer treatment.
研究领域:
纳米医学
·
肿瘤学
·
药学
·
免疫治疗
·
药物递送系统
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Yuchen Zhang,Shuang Feng,Jie Luo,Kaige Xu,Junfeng Guo,Xingyue Zhang,Mengxue Yuan,Qiang Luo,Yu Huang,Chaoqiang Fan,Kibret Mequanint,Donghui Zhu,Malcolm Xing,Shiming Yang
The cGAS-STING signaling pathway effectively activates antitumor immune responses and holds promise for overcoming drug resistance in hepatocellular carcinoma (HCC) immunotherapy. However, achieving specific activation of this pathway in HCC remains challenging. Here, it is introduced a single-metal-doped nanoplatform, ZMRPF, which leverages ferroptosis-induced mitochondrial DNA (mtDNA) release to stimulate cGAS-STING-mediated immune activation. ZMRPF initiates HCC ferroptosis by inducing high levels of lipid reactive oxygen species, leading to mitochondrial stress and the release of endogenous mtDNA. This mtDNA synergistically activates the cGAS-STING pathway, enhanced by immunoactivating Mn 2 ⁺ ions released from ZMRPF. Concurrently, the tumor antigens released during ferroptosis amplify the activity of antigen-presenting cells, creating a cascade that links ferroptosis with innate immunity. This cascade drives a robust systemic antitumor immune response, effectively reversing the immunosuppressive microenvironment of HCC. These results demonstrate the ability of ZMRPF to reshape the immune microenvironment of HCC and offer a promising strategy for next-generation tumor immunotherapy.
研究领域:
肿瘤学
·
免疫治疗
·
纳米医学
·
分子生物学
·
癌症免疫学
✓ 已验证
产品关联
DOI
高影响因子
PLoS Pathogens
·
2023
·Vol. 19
·期 4
·e1011314
·
IF 6.7
Lin Lv,Li Chai,Jie Wang,Mengge Wang,Danhui Qin,Hui Song,Yue Fu,Chunyuan Zhao,Jihui Jia,Wei Zhao,Mutian Jia
Stimulator-of-interferon gene (STING) is a vital element of the innate immune system against DNA viruses. Optimal activation of STING is crucial for maintaining immune homeostasis and eliminating invading viruses, and the oligomerization of STING is an essential prerequisite for STING activation. However, the mechanism of cGAMP-induced STING oligomerization in ER remains unclear. Selenoproteins are crucial for various physiological processes. Here, we identified that the endoplasmic reticulum (ER)-located transmembrane selenoprotein K (SELENOK) was induced during virus infection and facilitated innate immune responses against herpes simplex virus-1 (HSV-1). Mechanistically, SELENOK interacts with STING in the ER and promotes STING oligomerization, which in turn promotes its translocation from the ER to the Golgi. Consequently, Selenok deficiency suppresses STING-dependent innate responses and facilitates viral replication in vivo . Thus, the control of STING activation by selenium-mediated SELENOK expression will be a priming therapeutic strategy for the treatment of STING-associated diseases.
Selenoproteins are crucial for various physiological processes. Most selenoproteins locate in the cytoplasm and regulate redox pathways to protect cells from oxidative stress. However, the potential roles of transmembrane selenoproteins are largely unknown. Here, we identified Selenoprotein K (SELENOK), an ER-located transmembrane selenoprotein, as a physiological enhancer of STING-dependent antiviral innate immunity. SELENOK is upregulated during viral infection and enhances STING oligomerization to facilitate the activation of the cGAS-STING pathway and suppress viral replication. These results will be valuable for understanding the physiological roles of transmembrane selenoproteins in immunity. Furthermore, as aberrant STING activation has been linked to various pathological conditions, control of STING activity by SELENOK may be a prime therapeutic strategy.
研究领域:
免疫学
·
病毒学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）