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Acta Biomaterialia · 2023 · IF 9.7

A nanodrug simultaneously inhibits pancreatic stellate cell activation and regulatory T cell infiltration to promote the immunotherapy of pancreatic cancer

Rongze Wang,Keze Hong,Qiaoyun Zhang,Jianrong Cao,Tao Huang,Zecong Xiao,Yong Wang,Xintao Shuai

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense extracellular matrix flooded with immune suppressive cells, resulting in extremely poor clinical response to immunotherapy. It has been revealed that the activation of pancreatic stellate cells (PSCs) makes considerable contributions to the immunological “cold” tumor microenvironment (TME). Herein, we developed a polyamino acid-based nanodrug incorporating the PSC activation inhibitor calcipotriol and anti-CXCL12 siRNA. The nanodrug was easily prepared with a small particle size and is capable of penetrating pancreatic tumors to inactivate PSCs and downregulate CXCL12. The in vivo results of orthotopic pancreatic tumor treatment demonstrated that codelivery of calcipotriol and anti-CXCL12 siRNA remodeled the PDAC TME with reduced extracellular matrix and decreased immunosuppressive T cells . Eventually, the infiltration of cytotoxic T cells was increased, thereby acting with immune checkpoint blockade (ICB) therapy for immunologically “cold” pancreatic tumors. In the present study, we propose a promising paradigm to improve the immunotherapy outcome of PDAC using nanodrugs that synchronously inhibit PSC activation and regulatory T-cell infiltration. Statement of significance Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense extracellular matrix (ECM) that impedes the tumor infiltration of therapeutic agents and cytotoxic T lymphocytes, resulting in a poor clinical response to immunotherapy. In the present study, we proposed a promising approach for enhanced immunotherapy of pancreatic cancer. Specifically, a nanodrug incorporating calcipotriol and anti-CXCL12 siRNA was synthesized to synchronously inactivate matrix-producing pancreatic stellate cells and suppress the infiltration of regulatory T cells. The reduced ECM removed the pathological barrier, preventing nanodrug penetration and effector T-cell infiltration, leading to a conversion of the immunosuppressive “cold” microenvironment to a “hot” microenvironment, which eventually boosted the immunotherapy of anti-PD-1 antibodies in pancreatic cancer.

研究领域: 肿瘤学 · 药学 · 免疫学 · 纳米技术 · 癌症生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CytoJournal · 2024 · IF 2.5

Effect of 5-Aza-2’-deoxycytidine on T-cell acute lymphoblastic leukemia cell biological behaviors and PTEN expression

Yan Li,Zhenwei Jia,Xiaoyang Kong,Hongbo Zhao,Xiaoyan Liu,Guirong Cui,Jianmin Luo

Objective: We currently face a sharp increase of T-cell acute lymphoblastic leukemia (T-ALL) incidence and a challenge of unmasking its complex etiology. The deoxycytidine analog 5-Aza-2’-deoxycytidine (5-Aza-dC) is currently the most common nucleoside methyltransferase inhibitor. The objective of this study was to clarify the role of 5-Aza-dC in T-ALL cell biological behaviors and phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression. Material and Methods: T-ALL cell lines were divided into the experimental group with 5-Aza-dC solution treatment, and the control group without treatment. PTEN methylation was detected using methylation-specific polymerase chain reaction (MS-PCR). Following the measurement of cell proliferation, viability, apoptosis, invasion, migration, etc., quantitative reverse transcription-polymerase chain reaction (PCR) was conducted to detect PTEN, DNA methyl-transferases (DNMT1), DNMT3a, MBD2, and MeCP2 expressions; Western blot to detect PTEN, PI3K, AKT, and mTOR protein expressions. In addition, rescue experiments to inhibit and restore the expression of PTEN in different groups were performed for further identification of the results in the former parts. Results: MS-PCR results showed that in Jurkat cells, the target band was amplified using methylated primers for the PTEN gene promoter region; moreover, at 10 μmol/L of 5-Aza-dC for 24 h, PTEN methylation was completely removed without any un-methylated band observed. The experimental group had significantly lower cell proliferation and viability rates, higher apoptosis rates, decreased cell proportion in S phase, reduced invasion and migration; increased PTEN expression, decreased DNMT1, DNMT3a, MBD2, and MeCP2 mRNA expressions; and decreased PI3K, AKT, and mTOR protein expressions than those in the control group (all P < 0.05). Furthermore, according to the rescue experiment, silenced PTEN expression weakened the beneficial roles of 5-Aza-dC treatment, and resulted in significantly higher cell proliferation and viability rates, lower apoptosis rates, increased cell proportion in S phase, increased cell invasion and migration; decreased PTEN expression, elevated DNMT1, DNMT3a, MBD2, and MeCP2 mRNA expressions, and higher PI3K, AKT, and mTOR protein expressions (all P < 0.05). While restored PTEN expression enhanced functions of 5-Aza-dC treatment, leading to obviously lower cell proliferation and viability rates, higher apoptosis rates, increased cell proportion in G1 phase, and reduced cell invasion and migration; as well as increased PTEN expression, decreased DNMT1, DNMT3a, MBD2, and MeCP2 mRNA expressions, and lower PI3K, AKT, and mTOR protein expressions (all P < 0.05). Conclusion: Demethylation treatment with 5-Aza-dC can inhibit T-ALL cell malignant biological behaviors and enhance the sensitivity to chemotherapy agents possibly, which may be related to the inhibited expressions of DNMT1, DNMT3a, MBD2, and MeCP2, and restored expression activity of PTEN to negatively regulate the PI3K/AKT signal transduction. Our silencing and restoration of PTEN expressions further support our findings, highlighting that demethylation with 5-Aza-dC to restore the anti-tumor activity of the tumor suppressor gene PTEN may be a promising therapeutic option for treating T-ALL. Keywords: 5-Aza-2’-deoxycytidine, T-cell acute lymphoblastic leukemia, PTEN, Tumor cell biological behaviors, Demethylation

CAS / MDL: 8004-87-3
研究领域: 肿瘤学 · 分子生物学 · 血液学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CELL · 2019 · IF 36.216

Stress-Induced Metabolic Disorder in Peripheral CD4+ T Cells Leads to Anxiety-like Behavior

Ke-qi Fan,Yi-yuan Li,Hao-li Wang,Xin-tao Mao,Jin-xin Guo,Fei Wang,Ling-jie Huang,Yi-ning Li,Xiang-yu Ma,Zheng-jun Gao,Wei Chen,Dan-dan Qian,Wen-jin Xue,Qian Cao,Lei Zhang,Li Shen,Long Zhang,Chao Tong,Jiang-yan Zhong,Wei Lu,Ling Lu,Ke-ming Ren,Guisheng Zhong,Yuan Wang,Mingliang Tang,Xin-Hua Feng,Ren-jie Chai,Jin Jin

Summary Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4 + T cells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4 + T cells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4 + T cell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 accumulation in CD4 + T cells. Our study implicates a critical link between a purine metabolic disorder in CD4 + T cells and stress-driven anxiety-like behavior.

研究领域: 免疫学 · 神经科学 · 分子生物学 · 行为科学
✓ 已验证 DOI PubMed 高影响因子
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Advanced Science · 2025 · IF 14.1

Fragment Autoantigens Stimulated T-Cell-Immunotherapy (FAST) as a Fast Autologous Cancer Vaccine

Yuan Li,Huiqin Chen,Qiaofeng Shen,Yingshuang Liu,Pingping Li,Yuqi Ma,Yugang Wang,Shengkai Li,Xueqing Yan,Liyu Liu,Jianwei Shuai,Min Wu,Qi Ouyang,Feng-Ming (Spring) Kong,Gen Yang

Tumor cells often down-regulate antigen presentation and mount an immunosuppressive microenvironment, hindering successful cancer immunotherapy and vaccine development. Additionally, due to genomic instability, tumor cells are usually heterogeneous and constantly evolving. Therefore, vaccines need broad antigen coverage and rapid preparation. Here, a personalized whole tumor cell vaccine (TCV), termed fragment autoantigens stimulated T-cell-immunotherapy (FAST) is developed. In 7 h, tumor cells are treated with irradiation and cryoablation. Personalized fragmented antigens (FAs) from these treated cells are used as TCVs. In breast, colon, and melanoma mouse models, FAST achieved significant tumor regression, less metastasis, and longer survival. Notably, FAST outperforms other advanced TCVs, especially in curbing metastasis. Mechanistically, FAs activate efficient, broad-spectrum antigen presentation due to upregulation of immunogenic cell death, MHC-I, and damage-associated molecular patterns. Concurrently, FAST also enhances anti-tumor immunity by reshaping immune microenvironments. Analysis of clinical data shows FAST-associated proteins have prognostic and therapeutic value in patients with liver, stomach, rectal cancers, and melanoma. These results suggest FAST has high anti-tumor efficacy and potential as a personalized TCV platform. The relevant clinical trial NCT06756295 is under initiation with approval of ethics.

CAS / MDL: 115144-35-9
研究领域: 肿瘤学 · 免疫学 · 分子生物学 · 癌症研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL IMMUNOPHARMACOLOGY · 2025 · IF 4.7

Fibroblast growth factor 21 alleviated atopic march by inhibiting the differentiation of type 2 helper T cells

Dan Wang,Yimeng Zou,Tianqi Zhao,Weiyue Cao,Jiachi Han,Qing Wu,Zhitong Li,Xinyu Li,Peijing Liu,Lin Bai,Guiping Ren

Background The blood FGF21 expression has been previously suggested to increase in patients developing atopic dermatitis (AD) and asthma. However, its impact on atopic march is rarely analyzed. The present work focused on investigating the role of Fibroblast Growth Factor 21(FGF21) in atopic march mice and its underlying mechanisms. Methods The models were induced with Diisononyl phthalate (DINP) and OVA in wild-type C57BL/6 and FGF21 −/− mice. RAW264.7 cells were induced by LPS with/without FGF21 or KLB-SiRNA for in vitro analyses. Results The data indicated that there were more severe allergic reactions including IgE levels and the proportion of mast cells in the blood of FGF21 −/− mice in relative to WT model mice during the progression from AD to asthma. However, exogenous administration of FGF21 inhibited allergies. In this study, we reported that FGF21 mitigated AD-like lesions and Th1/2 or Th17/Treg cell imbalance in AD mice, and significantly decreased TSLP, IL-33, IL-4, IL-5, IL-13 and IL-17A expression on skin. During the asthma phase, FGF21 improved airway remodeling by downgrading inflammatory factors IL-4, IL-5, IL-13 and IL-17A; fibrotic markers α-SMA and Collagen I; and oxidative products MDA and ROS in wild-type model mice. Compared with WT model mice, the adverse consequences were aggravated in FGF21 −/− asthmatic mice. From the mechanistic perspective, FGF21 suppressed NF-κB/NLRP3, TGF-β1/Smad3 and JNK signaling pathways and increased Nrf2 expression in vivo and in vitro. In addition, β-Klotho knockdown attenuated the ameliorative impact of FGF21 on cellular damage. Blocking AMPKα in the LPS-treated RAW264.7 cells inhibited the reduction of FGF21 and the phosphorylation of JNK. Conclusions To conclude, FGF21 alleviated atopic march by inhibiting Th2/17 immune response, and reduced airway remodeling by regulating NF-κB/NLRP3, TGF-β1/Smad3 and AMPKα/JNK pathways. Moreover, this study provides a rationale and novel ideas for applying FGF21 in treating AD and asthma.

CAS / MDL: 56092-81-0 9005-65-6
研究领域: 免疫学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SEPARATION AND PURIFICATION TECHNOLOGY · 2021 · IF 7.312

High visible-light catalytic activity of Bis-PDI-T@TiO2 for activating persulfate toward efficient degradation of carbamazepine

Liwei Yang,Xuyang Hao,Dian Yu,Peng Zhou,Yaqi Peng,Yanyan Jia,Chuanliang Zhao,Jiaojie He,Chuanlang Zhan,Bo Lai

Due to the low concentrations of pharmaceuticals and personal care products (PPCPs), traditional water treatment processes are difficult to degrade them effectively. 2,5-bis (tributylstannyl) thiophene-perylene diimide-T@TiO 2 (Bis-PDI-T@TiO 2 ) composite photocatalyst is firstly prepared by the bisolvent phase transfer method and has a good ability to activate persulfate (PS) under visible light. 5 ppm Carbamazepine (CBZ) (a typical PPCPs) can be completely degraded by 1.0 g/L prepared photocatalyst and 1.0 mM PS within 30 min in the 0.1 wt% Bis-PDI-T@TiO 2 (PT 0.1 ) system under visible light. Four species of reactive oxidizing species were identified for CBZ degradation, including sulfate radical (SO 4 •− ), hydroxyl radical ( • OH), superoxide radical (O 2 •− ), and positive hole (h + ), and all contributed to CBZ degradation. Furthermore, the PT 0.1 photocatalyst exhibits the high stability and recyclability. This study also proposed the reaction mechanism of the Vis/PS/Bis-PDI-T@TiO 2 system and constructed a route of carbamazepine degradation in the coupled system.

研究领域: 环境科学 · 化学 · 水处理 · 催化
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IMMUNOLOGIC RESEARCH · 2025 ·Vol. 73 ·期 1 ·1-20 · IF 3.1

Piceatannol improves autoimmune hepatitis by inhibiting the immune activities of T cells and macrophages through binding with c-Jun

Xu Cong,Lu Chenqi,Wang Wu,Wang Zhimin,Qiu Yang,Han Min,Yang Jun,Li Shanglin

Autoimmune hepatitis (AIH) is an immune-mediated liver disease that currently lacks viable drug treatment methods. This study is to explore the role of piceatannol (PIC) in ConA-induced AIH and the related mechanisms. A mouse model of AIH was established by injecting ConA (i.v.), and PIC was administered as an intervention. The protective effect of PIC was evaluated by the liver function, liver pathology, and serum levels of inflammatory factors. Subsequently, network pharmacology was used to predict the pathways and targets of PIC in the treatment of AIH, and the predicted results were validated using flow cytometry, molecular docking, surface plasmon resonance (SPR) and so on. Finally, the immunosuppressive effect of PIC was further validated in a mouse heart transplantation model. PIC can improve liver function decline and reduce pathological liver damage, as well as inhibit the increase of serum inflammatory factor levels in mice with AIH induced by ConA. The protective effect is achieved by suppressing the immune activity of T cells and macrophages through binding to c-Jun. PIC can also extend the survival of cardiac allografts and inhibit acute rejection reactions. These results indicated that PIC can significantly improve ConA-induced AIH in mice by inhibiting the immune activity of T cells and macrophages through binding to c-Jun. PIC can also extend the survival of cardiac allografts in mice and inhibit acute rejection responses. The above results indicated that PIC may serve as a promising immunosuppressant and be effective for AIH.

CAS / MDL: 56-23-5
研究领域: 免疫学 · 肝病学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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POLYMER BULLETIN · 2016 ·Vol. 74 ·期 4 ·1091-1101 · IF 1.371

One-pot synthesis of molecular glass photoresists based on β-cyclodextrin containing a t-butyloxy carbonyl group for i-line lithography

Li Hu,Zhou Zhen,Liu Jingcheng,Xu Wenjia,Liu Ren,Liu Xiaoya

Positive chemically amplified molecular glass with pendant t -butyloxy carbonyl ( t -BOC) groups based on β-cyclodextrin (β-CD) was prepared. The β-CD derivatives were obtained from the reaction of β-CD and di- tert -butyl dicarbonate (DBDC) in the presence of 4-dimethylaminopyridine, and the protecting ratio was controlled using various feed amounts of DBDC. Fourier-transform infrared spectroscopy and proton nuclear magnetic resonance were employed to characterize the chemical structure, indicating that the synthesis was successful. Thermal behavior was characterized by thermogravimetric analysis; the results showed that the initial thermal decomposition temperature occurred at approximately 160 °C, which could satisfy the lithography process. Ultraviolet–visible spectrophotometer indicated that the t -BOC-protected β-CD derivatives had low absorbance at 365 nm wavelength. Additionally, X-ray diffraction analysis results showed that the β-CD derivatives had amorphous form, and exhibited excellent film-forming property. The photoresists consisting of different t -BOC protecting groups showed high sensitivity when exposed to 365 nm light and post-baked at 105 °C for 90 s, followed by developing in 2.38 wt% aqueous tetramethylammonium hydroxide solution at room temperature. An enhanced line and space positive patterns with 1 μm resolution were delineated according to digital microscope.

CAS / MDL: 1122-58-3
研究领域: 材料科学 · 光刻技术 · 有机化学
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JOURNAL OF APPLIED TOXICOLOGY · 2025 · IF 2.8

Maternal T-2 Mycotoxin Exposure Impairs Liver Function and Growth in Both Dams and Offspring in Mice

Kai Wang,Aneela Perveen,Jiakun Shen,Niaz Ali Kaka,Yansen Li,Dan Shen,Chunmei Li

T-2 mycotoxin is a highly toxic type A trichothecene mycotoxin that widely contaminates livestock feed, posing a serious threat to animal and human health. Long-term exposure can lead to immunosuppression, growth retardation, and liver damage, causing significant economic losses to the livestock industry. Offspring are particularly susceptible to maternal dietary influences during pregnancy and lactation. This research aimed to evaluate the impact of T-2 mycotoxin exposure on both dams and their pups. Thirty pregnant mice were randomly allocated into three groups ( n = 10). From gestational day 14 to lactational day 21, the dams received gavage doses of T-2 mycotoxin at concentrations of 0, 0.005, and 0.05 mg/kg/day. Randomly selected one male pup and one female pup from each dam were sacrificed on LD 1, 7, and 21; dams were dosed until the day they were sacrificed. T-2 mycotoxin decreased the relative body/organ weights of the dams and offspring ( p < 0.05). Moreover, T-2 mycotoxin-induced oxidative stress in dams and offspring increased the malondialdehyde content, which led to reduced activities of antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase, and total antioxidant capacity in the serum and liver ( p < 0.05). T-2 mycotoxin induced histomorphological changes in the liver and early involution of the mammary gland acini in dams. The concentrations of liver-metabolizing enzymes such as glutamic oxaloacetic transaminase and glutamic pyruvic transaminase increased in offspring ( p < 0.05). The serum insulin-like growth factor-1 level in offspring was decreased, which may impair the development of vital organs such as the liver, kidneys, and spleen in offspring. Consequently, the body weight and length of the offspring of exposed dams decreased. This study revealed that T-2 mycotoxin exposure during late gestation and entire lactation harms dams, damages mammary gland acini, alters liver biochemistry, induces oxidative stress, and delays offspring growth while also impairing maternal weight gain during lactation.

CAS / MDL: 8001-30-7
研究领域: 毒理学 · 生殖生物学 · 发育生物学 · 肝脏病学 · 营养毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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World Journal of Clinical Oncology · 2024 · IF 2.6

Gene signatures to therapeutics: Assessing the potential of ivermectin against t(4;14) multiple myeloma

Yang Song,Hao-Jun Zhang,Xia Song,Jie Geng,Hong-Yi Li,Li-Zhong Zhang,Bo Yang,Xue-Chun Lu

BACKGROUND Multiple myeloma (MM) is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow. The translocation, (t)(4;14), results in high-risk MM with limited treatment alternatives. Thus, there is an urgent need for identification and validation of potential treatments for this MM subtype. Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets. AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14) MM subtype by employing a comprehensive approach. METHODS The transcriptional signature of t(4;14) MM was sourced from the Gene Expression Omnibus. Two datasets, {"type":"entrez-geo","attrs":{"text":"GSE16558","term_id":"16558"}} GSE16558 and {"type":"entrez-geo","attrs":{"text":"GSE116294","term_id":"116294"}} GSE116294 , which included 17 and 15 t(4;14) MM bone marrow samples, and five and four normal bone marrow samples, respectively. After the differentially expressed genes were identified, the Cytohubba tool was used to screen for hub genes. Then, the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Using the STRING database and Cytoscape, protein–protein interaction networks and core targets were identified. Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis, respectively. RESULTS In this study, a total of 258 differentially expressed genes with enriched functions in cancer pathways, namely cytokine receptor interactions, nuclear factor (NF)-κB signaling pathway, lipid metabolism, atherosclerosis, and Hippo signaling pathway, were identified. Ten hub genes ( cd45, vcam1, ccl3, cd56, app, cd48, btk, ccr2, cybb, and cxcl12 ) were identified. Nine drugs, including ivermectin, deforolimus, and isoliquiritigenin, were predicted by the Connectivity Map database to have potential therapeutic effects on t (4;14) MM. In molecular docking, ivermectin showed strong binding affinity to all 10 identified targets, especially cd45 and cybb . Ivermectin inhibited t(4;14) MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro. Furthermore, ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14) MM cells. CONCLUSION Collectively, the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14) MM diagnosis and treatment, with ivermectin emerging as a potential therapeutic alternative.

研究领域: 肿瘤学 · 药理学 · 分子生物学 · 生物信息学 · 癌症研究
✓ 已验证 DOI PubMed 高影响因子
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ACS Nano · 2025 · IF 16

Zinc Ion-Coordinated Sericin Calcium Phosphate Nanovaccines Induce Hyperactive Dendritic Cells and Synergistic Activation of T Cells for Cancer Immunotherapy

Lei Huang,Xinbo Li,Hongyan Zhang,Feng Liu,Zheng Dai,Fang Xiao,Lin Wang,Zheng Wang

Peptide-based neoantigen vaccines are promising cancer immunotherapy strategies because of their capability to induce durable tumor-specific immune responses. However, insufficient neoantigen-specific T-lymphocyte activation greatly limits their clinical efficacy. Here, we developed sericin-coordinated zinc ion-modified calcium phosphate (CP) nanovaccines that codeliver tumor antigen peptides and a Toll-like receptor 9 agonist (SZCP/APs-CpG) for potentiating antigen-specific T cell immunity. SZCP/APs-CpG nanovaccines could yield efficient codelivery of antigen peptides and adjuvants to dendritic cells (DCs) in draining lymph nodes (dLNs), induce hyperactive DCs depending on the inflammasome-dependent interleukin-1β secretion, and coordinate the released Zn2+-induced T cell activation to elicit robust and durable antigen-specific T cell immune responses. Vaccination with SZCP/APs-CpG exhibited potent anticancer efficacy and superior safety in multiple murine cancer models and significantly protected against B16-OVA tumor rechallenge and eradicated orthotopic colon cancer in mice when combined with immune checkpoint blockade. Thus, our work presents an efficient and versatile nanovaccine platform for boosting antigen-specific T cell activation for cancer immunotherapy.

研究领域: 免疫学 · 肿瘤学 · 纳米医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Signal Transduction and Targeted Therapy · 2025 ·Vol. 10 ·期 1 ·1-17 · IF 52.7

Condensate nanovaccine adjuvants augment CD8+ T-Cell-dependent antitumor immunity through mtDNA leakage-triggered cGAS-STING axis activation

Tang Yu,Luo Zhiyuan,Ma Zhanni,Han Lingling,Zhou Yurong,Liang Tianci,Yang Kangsen,Zhao Lei,Chen Xiaoyuan,Zhang Pengfei

The variety and functionality of current clinical vaccine adjuvants remain limited. Conventional aluminum-based adjuvants predominantly induce Th2-biased humoral immunity but exhibit a limited capacity to elicit Th1-mediated cellular immune responses, particularly tumor antigen-specific cytotoxic CD8 + T lymphocytes (CTLs), which are essential for effective cancer vaccine performance. Inspired by natural biomolecular condensates, we developed a versatile noncovalent protein self-assembly strategy distinct from traditional approaches requiring structural domain modifications or bifunctional crosslinkers. Our methodology employs amphiphilic molecules (sodium myristate/SMA and sodium dodecyl thiolate/SDT) as molecular bridges to mediate protein‒protein interactions through hydrophobic forces and disulfide bond formation. This process generates nanoscale protein condensate (PCD) vaccines with exceptional stability. As a novel adjuvant system, these synthetic condensates significantly enhance antigen cross-presentation by optimizing key parameters: antigen loading capacity, lymph node targeting, cytosolic delivery, and lysosomal escape. Consequently, they induce robust antigen-specific CTL responses and humoral immunity, demonstrating potent antitumor efficacy. Importantly, we found that the synthetic protein condensate (PCD) alone can act as a nanoadjuvant. By increasing mitochondrial membrane permeability, PCD induces mitochondrial DNA leakage into the cytosol, activating the cGAS‒STING pathway and promoting DC maturation. This safe and scalable platform eliminates the need for complex covalent modifications or genetic engineering, and it facilitates the design of diverse modular antigens, including neoantigens and viral antigens. Given its straightforward manufacturing process and superior immunogenicity, this synthetic PCD vaccine adjuvant has significant potential for clinical application and translation.

研究领域: 免疫学 · 肿瘤学 · 纳米医学 · 分子生物学 · 转化医学 · 疫苗学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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