Nature Communications
·
2024
·Vol. 15
·期 1
·1-20
·
IF 14.7
Huang Zhusheng,Huang Shiqian,Song Simin,Ding Yankui,Zhou Hao,Zhang Shaoyin,Weng Lixing,Zhang Ying,Hu Yiqiao,Yuan Ahu,Dai Yunlu,Luo Zhimin,Wang Lianhui
The irradiated tumor itself represents an opportunity to establish endogenous in situ vaccines. However, such in situ cancer vaccination (ISCV) triggered by radiation therapy (RT) alone is very weak and hardly elicits systemic anticancer immunity. In this study, we develop two-dimensional risedronate-manganese nanobelts (RMn-NBs) as an adjuvant for RT to address this issue. RMn-NBs exhibit good T 2 magnetic resonance imaging performance and enhanced Fenton-like catalytic activity, which induces immunogenic cell death. RMn-NBs can inhibit the HIF-1α/VEGF axis to empower RT and synchronously activate the cGAS/STING pathway for promoting the secretion of type I interferon, thereby boosting RT-triggered ISCV and immune checkpoint blockade therapy against primary and metastatic tumors. RMn-NBs as a nano-adjuvant for RT show good biocompatibility and therapeutic efficacy, presenting a promising prospect for cancer radiotherapy and immunotherapy.
研究领域:
癌症研究
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纳米技术
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免疫治疗
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放射治疗
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Pengfei Yuan,Xiaodie Yan,Xiaoqing Zong,Xiaodi Li,Caiqi Yang,Xinjie Chen,Yuchao Li,Yaoqi Wen,Tianci Zhu,Wei Xue,Jian Dai
Cancer immunotherapy has emerged as a promising approach to cancer treatment in recent years. The physical and chemical properties of nanocarriers are critical factors that regulate the immune activation of antigen-presenting cells (APCs) in the tumor microenvironment (TME). Herein, we extensively investigated the behavior of liposome nanoparticles (Lipo-NPs) with different elasticities, focusing on their interaction with immune cells and their transport mechanisms from tumors to tumor-draining lymph nodes (tdLNs). Successfully preparing Lipo-NPs with distinct elastic properties, their varied behaviors were observed, concerning immune cell interaction. Soft Lipo-NPs exhibited an affinity to cell membranes, while those with medium elasticity facilitated the cargo delivery to macrophages through membrane fusion. Conversely, hard Lipo-NPs enter macrophages via classical cellular uptake pathways. Additionally, it was noted that softer Lipo-NPs displayed superior transport to tdLNs in vivo, attributed to their deformable nature with lower elasticity. As a result, the medium elastic Lipo-NPs with agonists (cGAMP), by activating the STING pathway and enhancing transport to tdLNs, promoted abundant infiltration of tumor-infiltrating lymphocytes (TILs), leading to notable antitumor effects and extended survival in a melanoma mouse model. Furthermore, this study highlighted the potential synergistic effect of medium elasticity Lipo-NPs with immune checkpoint blockade (ICB) therapy in preventing tumor immune evasion. These findings hold promise for guiding immune-targeted delivery systems in cancer immunotherapy, particularly in vaccine design for tdLNs targeting and eradicating metastasis within tdLNs.
研究领域:
生物医学工程
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免疫学
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纳米技术
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癌症研究
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Han Yan,Wenting Cheng,Siyuan Qin,Jing Zuo,Lei Li,Jing Zhang,Qinxia Chang,Yonghao Yan,Shiqi Wang,Canhua Huang,Haiyuan Zhang
The blood–brain barrier (BBB) caused limited drug accumulation and programmed death-ligand 1 (PD-L1) compromised immunosuppressive microenvironment are bottlenecks in glioblastoma multiforme (GBM) treatment. Herein, we bioengineered a human heavy chain nanoferritin (HTE NPs) for GBM-specific delivery and efficient immunotherapy. To achieve targeted mitochondrial metabolic regulation, we connected triphenylphosphonium (TPP) with the photosensitive agent IR780 to form T780, which self-assembles with esomeprazole magnesium (EM) and human H-ferritin (HFn) to obtain HTE NPs. HFn endows HTE NPs with BBB penetration and specific site-targeting capabilities, thereby enhancing tumor accumulation and pH-responsive release within GBM cells. T780 subsequently induces mitochondrial damage, activating the AMP-dependent protein kinase (AMPK) pathway and blocking the transmission of T-cell inhibitory signals through the phosphorylation of PD-L1, thereby promoting T-cell activation. Moreover, EM inhibits the release of extracellular vesicles (EVs), reducing the inhibitory effect of PD-L1 on circulating T cells. Furthermore, mitochondrial impairment-induced mitochondrial DNA (mtDNA) leakage activates the cGAS-STING signaling pathway, inducing the maturation of dendritic cells (DCs), recruiting supportive immune cells to clear GBM cells, and improving the immunosuppressive microenvironment. Therefore, HTE NPs not only achieve efficient tumor accumulation but also facilitate the activation immune response, providing a promising strategy for the clinical treatment of GBM.
研究领域:
肿瘤学
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神经科学
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纳米技术
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免疫学
✓ 已验证
DOI
高影响因子
Small Methods
·
2020
·Vol. 4
·期 3
·1900799
·
IF 12.13
Yan Peng Jia,Kun Shi,Jin Feng Liao,Jin Rong Peng,Ying Hao,Ying Qu,Li Juan Chen,Li Liu,Xia Yuan,Zhi Yong Qian,Xia Wei Wei
The safety issues and immunological effects of nanosized materials have drawn considerable attention. Gold nanorods (Au NRs) have promising applications in biomedical diagnosis and therapy, but their biosafety and the mechanism underlying in vivo toxicity still remain to be explored. In this study, cetyltrimethylammonium bromide (CTAB) capped Au NRs and PEG modified Au NRs are both prepared, the cytotoxicity evaluation indicates that CTAB-Au NRs of different ratios all exhibit cytotoxicity while PEG-Au NRs show improved biocompatibility. Furthermore, it is investigated how the surface characteristics influence toxical effects of Au NRs both in vitro and in vivo. It is found that CTAB-Au NRs can induce acute cell necrosis, which results in the leakage of damage associated molecular patterns (DAMPs) such as mitochondrial DNA (mtDNA), subsequently triggering pulmonary inflammation. It is also revealed that the inflammation caused by CTAB-Au NRs is probably mediated by the stimulator of interferon genes (STINGs) signaling pathway. This study explores the cytotoxicity and inflammatory toxicity of CTAB-Au NRs, and how the surface modification affects the toxicity. The molecular pathways for the induction of pulmonary inflammation in vivo are further characterized. These findings might be of importance for designing safer and better gold-based nanomaterials in the future.
研究领域:
纳米技术
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毒理学
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免疫学
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生物医学工程
✓ 已验证
DOI
高影响因子
Small
·
2025
·
IF 12.1
Weitao Wang,Haitao Wu,Xuan Zhang,Yang Hong,Shi Tao,Xiangjing Cao,Shipeng Wang,Lisha Zha,Zhengbao Zha
Using entire tumor cells or tissues that display both common and patient-specific antigens can potentially trigger a comprehensive and long-lasting anti-tumor immune response. However, the limited immunogenicity, low uptake efficiency, and susceptibility to degradation of whole-component antigens present significant challenges. In this study, we employed tumor lysates (TLs) as whole-component antigens, in conjunction with MgAl-layered double hydroxide (MA) as nanoadjuvants and Mn 2+ as immunostimulants, to create personalized MMAT (Mn 2+ -MA-TLs) nanovaccines. After subcutaneous injection of MMAT nanovaccines, the high local concentrations of TLs and Mn 2+ facilitated the recruitment and activation of antigen-presenting cells (APCs), thereby inducing a robust adaptive immune response. Remarkably, MMAT nanovaccines enabled lysosomal escape, enhanced antigen cross-presentation, and activated the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in APCs. Furthermore, MMAT nanovaccines, when combined with the anti-TIGIT monoclonal antibody (aTIGIT), an immune checkpoint inhibitor, not only stimulated T-cell-based adaptive anti-tumor immune responses but also activated the NK-cell-based innate anti-tumor immunity, effectively suppressing tumor growth, recurrence, and metastasis. Thus, the ternary MMAT nanovaccines developed here introduced a pioneered paradigm for the rapid preparation of whole-component tumor antigens with nanoadjuvants and immunostimulants into nanovaccines, offering new prospects for clinical immunotherapies.
研究领域:
癌症免疫疗法
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免疫学
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纳米医学
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肿瘤生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Xiejun Zhao,Xiangchuan Qin,Ruizhe Wang,Yawen Wang,Yinli He,Yuchen Wang,Kefeng Li,Peipei Zhang,Chen Yang,Menghan Wang,Yingtong Dong,Xue Shi,Jia Ma,Jiye Zhang,Xiaojiao Li
Inefficient priming, poor recruitment, and inadequate reinvigoration of T cells challenges the therapy of PD-L1-resistant tumors. Herein, a pH-responsive charge-reversal nanoplatform integrating coactivator-associated arginine methyltransferase 1 (CARM1) inhibitor (iCARM1) and poliovirus receptor siRNA (siPVR) is developed. Upon tumor penetration, iCARM1 released in tumor cells facilitates T cell priming by epigenetically activating cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling-mediated dendritic cell maturation. Meanwhile, in T cells, iCARM1 facilitates their recruitment by upregulating CXC-chemokine receptor 3 (CXCR3) expression. The released siPVR silences pvr to reinvigorate T cells. This epigenetic nanoagonist induces a robust immune response, dramatically suppresses tumor growth, metastasis, and relapse, and confers durable protection against secondary tumor challenge. Multiple PD-L1-resistant models demonstrate the broad applicability of this strategy. This study thus represents an innovative approach for facilitating multilevel T cell responses to combat PD-L1-resistant tumors.
研究领域:
癌症免疫治疗
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纳米医学
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表观遗传学
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分子生物学
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免疫学
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信号转导
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RNA干扰
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Ziang Li,Jincheng Tang,Liang Zhou,Jiannan Mao,Wei Wang,Ziyan Huang,Lichen Zhang,Jie Wu,Xinzhao Jiang,Zhouye Ding,Kun Xi,Feng Cai,Yong Gu,Liang Chen
The extracellular matrix (ECM) stores signaling molecules and facilitates mechanical and biochemical signaling in cells. However, the influence of biomimetic “rejuvenation” ECM structures on aging- and degeneration-related cellular activities and tissue repair is not well understood. We combined physical extrusion and precise “on–off” alternating cross-linking methods to create anisotropic biomaterial microgels (MicroRod and MicroSphere) and explored how they regulate the cell activities of the nucleus pulposus (NP) and their potential antidegenerative effects on intervertebral discs. NP cells exhibited aligned growth along the surface of the MicroRod, enhanced proliferation, and reduced apoptosis. This suggests an adaptive cellular response involving adhesion and mechanosensing, which causes cytoskeletal extension via environmental cues. NP cells maintain nuclear membrane integrity through the YAP/TAZ pathway, which activates the cGAS-STING pathway to rectify the aging mechanisms. In vivo, MicroRod carries NP cells and reduces inflammatory factor and protease secretion in degenerated intervertebral discs, inhibiting degeneration and promoting NP tissue regeneration. Our findings highlight the role of mechanical stress in maintaining cellular activity and antiaging effects in harsh environments, providing a foundation for further research and development of antidegenerative biomaterials.
研究领域:
生物材料
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组织工程
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力学生物学
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细胞衰老
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退行性疾病
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Shiyu Zhang,Siyi Li,Xiucheng Zhao,Wubin Lv,Yuxuan Zhao,Lei Zhong,Shili Gai,He Ding,Ruizheng Liang,Piaoping Yang
Ion-overload-mediated pyroptosis can enhance cytotoxic T-cell infiltration and systemic immunity, presenting a promising strategy to strengthen immunotherapy efficacy. However, the low frequency of pro-inflammatory immune cells and the immunosuppressive tumor network pose substantial challenges to achieving potent immunogenic cell death. This study designs a multiphase phase-transition nano-disruptor (V-MoS 2 &CaF 2 @HA), inspired by ionic interference and metabolic inhibition, to target multiple immunosuppressive mechanisms in tumors. Vanadium-doping engineering induces the coexistence of the 2H (semiconducting) and 1T (metallic) phases, maximizing the ability of piezocatalysts to enhance charge-carrier mobility. Critically, V-MoS 2 with its ultrathin, asymmetrical layered architecture, reinforces the piezoelectric response by promoting band bending and charge-carrier separation, thereby establishing favorable conditions for efficient electron–hole separation and reactive oxygen species generation. Concurrently, calcium-ion self-amplifying leakage and hydrogen sulfide liberation collectively create an “ion-interference–metabolic-hijacking” effect that induces oxidative stress, amplifies innate immune cGAS–STING pathway activation, and triggers a pyroptosis–apoptosis cross-death effect and immune activation. Thus, the study offers a straightforward strategy to achieve antitumor immunity through STING pathway activation and provides a new avenue to robustly activate immunogenic cell death for tumor treatment.
研究领域:
纳米医学
·
癌症免疫治疗
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生物医学工程
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活性氧信号传导
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肿瘤微环境
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免疫原性细胞死亡
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2023
·Vol. 8
·期 1
·1-16
·
IF 39.3
Cui Bopei,Song Lifang,Wang Qian,Li Kelei,He Qian,Wu Xing,Gao Fan,Liu Mingchen,An Chaoqiang,Gao Qiushuang,Hu Chaoying,Hao Xiaotian,Dong Fangyu,Zhou Jiuyue,Liu Dong,Song Ziyang,Yan Xujia,Zhang Jialu,Bai Yu,Mao Qunying,Yang Xiaoming,Liang Zhenglun
With the continuous in-depth study of the interaction mechanism between viruses and hosts, the virus has become a promising tool in cancer treatment. In fact, many oncolytic viruses with selectivity and effectiveness have been used in cancer therapy. Human enterovirus is one of the most convenient sources to generate oncolytic viruses, however, the high seroprevalence of some enteroviruses limits its application which urges to exploit more oncolytic enteroviruses. In this study, coxsackievirus B5/Faulkner (CV-B5/F) was screened for its potential oncolytic effect against non-small cell lung cancers (NSCLCs) through inducing apoptosis and autophagy. For refractory NSCLCs, DNA-dependent protein kinase (DNA-PK) or ataxia telangiectasia mutated protein (ATM) inhibitors can synergize with CV-B5/F to promote refractory cell death. Here, we showed that viral infection triggered endoplasmic reticulum (ER) stress-related pro-apoptosis and autophagy signals, whereas repair for double-stranded DNA breaks (DSBs) contributed to cell survival which can be antagonized by inhibitor-induced cell death, manifesting exacerbated DSBs, apoptosis, and autophagy. Mechanistically, PERK pathway was activated by the combination of CV-B5/F and inhibitor, and the irreversible ER stress-induced exacerbated cell death. Furthermore, the degradation of activated STING by ERphagy promoted viral replication. Meanwhile, no treatment-related deaths due to CV-B5/F and/or inhibitors occurred. Conclusively, our study identifies an oncolytic CV-B5/F and the synergistic effects of inhibitors of DNA-PK or ATM, which is a potential therapy for NSCLCs.
研究领域:
肿瘤学
·
病毒学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Yingpei Yao,Zijie Lu,Chao Fang,Shuyue Chang,Yongjun Wu,Xiang Li,Junwei Zhao,Yike Fu,Xiang Li
Chemotherapy remains a mainstream cancer therapy but is hindered by severe side effects and limited durable cancer control. Smart nanomedicines that integrate prodrug delivery and immune modulation may offer potential opportunities to tackle the daunting challenges. Herein, an acid-responsive nanocarrier (ZZTA) consisting of ZnO 2 , ZIF-8, and Zn-tannic acid is developed. A phenylboronic ester prodrug (BDOX) is synthesized and integrated with ZZTA, creating a multifunctional nano-prodrug, ZZTA-BDOX. The yolk-shell structure of ZZTA prevents premature decomposition of ZnO 2 during circulation, and enables sustained release of Zn 2+ and H 2 O 2 in response to the acidic tumor microenvironment. The generated H 2 O 2 subsequently activates BDOX, releasing cytotoxic DOX intracellularly. Meanwhile, the Zn 2+ released enhances cGAS-STING signaling, promoting dendritic cell maturation and T cell priming, which results in clear systemic antitumor immune responses. The in vivo study demonstrates that ZZTA-BDOX nano-prodrug not only enables efficient tumor inhibition but also suppresses metastasis through immune activation.
研究领域:
纳米医学
·
癌症免疫治疗
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药物递送系统
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生物无机化学
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肿瘤微环境
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前药设计
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Chengyao Huang,Ke Zhang,Yu Ren,Xihong Liu,Yan Li,Bangliu Yang,Peiran Chen,Mingyue Zhang,Xiaotong Lu,Yuhong Zhuo,Chao Qi,Kaiyong Cai
Tumor immunotherapy has gained more and more attention in tumor treatment. However, the accumulation of lactic acid in tumor tissue inhibits the response of immune cells to form an immunosuppressive microenvironment (ISME). To reverse the ISME, an acid-responsive nanoplatform (termed as MLLN@HA) is reported for synergistically enhanced tumor immunotherapy. MLLN@HA is constructed by the co-loading of lactate oxidase (LOX) and DNA repair inhibitor (NU7441) in a manganese-doped layered double hydroxide (Mn-LDH), and then modified with hyaluronic acid (HA) for tumor-targeted delivery. After endocytosis by tumor cells, MLLN@HA decomposes and releases LOX, NU7441 and Mn 2+ ions in the acidic tumor microenvironment. The released LOX catalyzes the conversion of lactic acid into hydrogen peroxide (H 2 O 2 ), which not only alleviates the ISME, but also provides reactants for the Mn 2+ -mediated Fenton-like reaction to enhance chemodynamic therapy (CDT). Released NU7441 prevents CDT-induced DNA damage from being repaired, thereby increasing double-stranded DNA (dsDNA) fragments within tumor cells. Importantly, the released Mn 2+ ions enhance the sensitivity of cyclic GMP-AMP synthase (cGAS) to dsDNA fragments, and activate the stimulator of interferon genes (STING) to induce an anti-tumor immune response. Such an orchestrated immune-boosting strategy ultimately achieves effective tumor growth inhibition and prevents tumor lung metastasis. Statement of significance To improve the efficacy of tumor immunotherapy, an innovative acid-responsive MLLN@HA nanoplatform was developed for synergistically enhanced tumor immunotherapy. The MLLN@HA actively targets to tumor cells through the interaction of HA with CD44, and then degrades to release LOX, NU7441 and Mn 2+ ions in the acidic tumor microenvironment. The released LOX generates H 2 O 2 for the Mn 2+ -mediated Fenton reaction and reverses the ISME by consuming lactate. NU7441 prevents DNA damage repair, leading to an increased concentration of free DNA fragments, while Mn 2+ ions activate the cGAS-STING pathway, enhancing the systemic anti-tumor immune response. The orchestrated immune-boosting nanoplatform effectively inhibits tumor growth and lung metastasis, presenting a promising strategy for cancer treatment.
研究领域:
癌症研究
·
免疫治疗
·
纳米医学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2024
·
IF 11.4
Dongwei Guan,Pengju Huang,Xinlei Liu,Qing Li,Xiaoxun Zhang,Nan Liu,Yong Wang,Ying Wan,Jin Chai,Shiying Cai,Rui Chen,Zhijia Ye
Introduction Niemann-Pick C1 (NPC1), a lysosomal cholesterol transport protein, is required for efficient efferocytosis. Patients with Npc1 mutation are frequently accompanied with hepatic symptoms, including hepatomegaly, elevated liver transaminases, or even acute liver failure, but the pathogenic mechanism remains unknown. Objectives Our work aims to characterize the functional role of myeloid NPC1 in liver injury and elucidate its underlying mechanism. Methods Analyses of injured livers from patients with liver diseases and mouse models were conducted to examine NPC1 expression. Myeloid cell-specific Npc1 knockout mice were constructed to determine the functional role of macrophage NPC1 in liver injury. Isolated macrophages were subjected to in vitro mechanistical assays. Results We found that NPC1 is mainly expressed in hepatic macrophages. Its mRNA and protein expression are significantly elevated in injured livers from both patients and mouse models. Tissue-specific deletion of myeloid Npc1 increased liver inflammation, levels of serum liver function enzymes, and liver fibrosis in mouse models of liver injury induced by carbon tetrachloride (CCl 4 ) injection and methionine-and-choline-deficient (MCD) diets. Further analyses indicate that Npc1 deficiency in mouse models of liver injury resulted in increased levels of serum HMGB1 and mitochondrial DNA, promoted hepatic macrophage proinflammatory activation, M1 polarization, led to overproduction of hepatic inflammatory cytokines/chemokines, e.g. CCL2 and STING/NFκB pathway activation. In vitro mechanistical studies reveal that Npc1 -deficient macrophages exhibited inefficient efferocytosis, partly due to impaired cargo degradation. Conclusions These findings indicate that elevated expression of myeloid NPC1 in liver diseases protects liver from injury by promoting macrophage efferocytosis of damaged cells. Dysfunction of NPC1 aggravates liver injury, suggesting that NPC1 may be a potential therapeutic target for treating liver diseases.
研究领域:
肝病学
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免疫学
·
细胞生物学
·
病理学
✓ 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）