Advanced Science
·
2026
·
IF 14.1
Yao Xiao,Yuxuan Yang,Haosen Qiu,Jia Yang,Hao Liang,Zhaojun Jiang,Xiao Tong,Yongying Li,Qunfeng Huang,Jiaming Wu,Tian Lin,Jiang Yu,Min Liang
Colorectal cancer (CRC) remains therapeutically challenging due to high metastasis, recurrence, and immunotherapy resistance driven by tumor microenvironment-mediated immune evasion. Immunogenic cell death (ICD) offers a promising strategy to reshape the immune microenvironment, yet existing ICD inducers suffer from poor targeting efficiency and insufficient death signal release. Here, we constructed a calcium overload-based smart nanosystem, HA-HAP@CUR, to achieve highly efficient ICD induction via a triple-effect mechanism: hyaluronic acid (HA)-mediated CD44 targeting enables tumor-selective accumulation; pH-responsive hydroxyapatite (HAP) degradation releases Ca 2+ in the acidic tumor microenvironment; and curcumin (CUR) amplifies intracellular calcium overload by promoting endoplasmic reticulum Ca 2+ release, collectively establishing a positive feedback loop disrupting calcium homeostasis. Mechanistically, calcium overload induces mitochondrial membrane potential dissipation and sustained mPTP opening, triggering mitochondrial oxidative stress and energy metabolic disorders. This mitochondrial crisis concurrently activates caspase-3, GSDMD, and RIPK1, synergistically initiating apoptosis, pyroptosis, and necroptosis, ultimately converging into PANoptosis with potent immunostimulatory potential. This strategy, encompassing targeted accumulation, calcium storm activation, and multi-modal cell death synergy, provides a biologically precise approach to overcoming immunotherapy resistance in CRC.
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Hanzhe Liu,Zhenan Liu,Weilian Liang,Hokeung Tang,Lili Yu,Tong Wang,Lan Liu,Qingli Chen,Jia-Wei Wang,Xian-Zheng Zhang,Guo-Feng Luo,Zhengjun Shang
Combination of multiple immune activation pathways that can modulate different immune axes in coordination has been found extremely effective in amplifying immunotherapy. In this study, by using the naturally occurring tea leaf-derived nanovesicles (TDNVs), we prepare an all-in-one multifunctional immunotherapeutic nanomedicine (denoted as DFeTNVs) by co-loading chemotherapeutic drug, doxorubicin (DOX), into a ferric-engineered TDNVs. Owing to the acid-triggered responsiveness, the loaded cargoes (DOX and Fe 3+ ) would be released in the tumor acidic microenvironment to elicit DOX-mediated immunogenic cell death (ICD), which is further enhanced by the ferric ions-mediated Fenton reaction. Strikingly, the inherent surface galactose of DFeTNVs could promote specific cellular uptake of macrophages through galactose-type lectin-mediated endocytosis so as to deliver Fe 3+ inside macrophages for potentiating the polarization of M2-like tumor-associated macrophages (TAMs) into M1 phenotype, thereby boosting the macrophage-mediated phagocytosis and T cell activation. All these contribute to evoking a strong anticancer immune response, especially in combination with anti-PD-L1 antibody, to inhibit tumor growth. The present work provides a delicate design integrated with multiple functions (i.e., drug loading, metal chelation, intrinsic targeting) without using excessive chemical ligands or complex synthetic processes, promising the feasibility of this immunotherapeutic nanosystem for future clinical applications.
研究领域:
肿瘤学
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免疫学
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纳米医学
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DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Panpan Song,Bingjie Wang,Qi Pan,Tianze Jiang,Xiangyan Chen,Miao Zhang,Jiaojiao Tao,Xia Zhao
Programmed cell death-ligand 1 (PD-L1) small interfering RNA (siRNA) achieves tumor immunotherapy by restoring the immune response of T cells, but the efficacy of PD-1/PD-L1 monotherapy is relatively low. While immunogenic cell death (ICD) can improve the response of most tumors to anti-PD-L1 and enhance tumor immunotherapy. Herein, a targeting peptide GE11-functionalized dual-responsive carboxymethyl chitosan (CMCS) micelle (G-CMssOA) is developed for simultaneous delivery of PD-L1 siRNA and doxorubicin (DOX) in a complex form of DOX·PD-L1 siRNA (D&P). The complex-loaded micelles (G-CMssOA/D&P) have good physiological stability and pH/reduction responsiveness, and improve the intratumoral infiltration of CD4 + and CD8 + T cells, reduce Tregs (TGF-β), and increase the secretion of immune-stimulatory cytokine (TNF-α). The combination of DOX-induced ICD and PD-L1 siRNA-mediated immune escape inhibition significantly improves anti-tumor immune response and inhibits tumor growth. This complex delivery strategy provides a new approach for effectively delivering siRNA and enhancing anti-tumor immunotherapy.
研究领域:
药学
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免疫学
·
癌症研究
·
纳米技术
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PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Ke Zhang,Chengyao Huang,Yu Ren,Mingyue Zhang,Xiaotong Lu,Bangliu Yang,Peiran Chen,Shiyao Guo,Xueqian Wang,Yuhong Zhuo,Chao Qi,Kaiyong Cai
Tumor immunotherapy represents one of the most promising strategies for combating tumors by activating the immune system, harnessing anti-tumor immune cells to eliminate tumor cells, and preventing tumor recurrence and metastasis. However, clinical data indicate that the anti-tumor immune response is often inadequate in many cancer patients, resulting in the failure of tumor immunotherapy. Herein, we report a manganese (Mn)-based nanoadjuvant (denoted as BMP-Au) aimed at synergistically enhancing anti-tumor immune responses in breast cancer therapy through disulfidptosis-induced immunogenic cell death and Mn-mediated cGAS-STING pathway activation. BMP-Au is synthesized using bovine serum albumin as a biotemplate for biomimetic mineralization of manganese phosphate nanosheets, followed by the deposition of gold nanoparticles (Au NPs) on their surface. By exploiting the glucose oxidase-like activity of Au NPs alongside the Fenton-like reaction facilitated by Mn 2+ , BMP-Au orchestrates a cascade catalytic reaction that generates reactive oxygen species from glucose. This process not only initiates disulfidptosis but also leads to DNA fragmentation crucial for activating the cGAS-STING pathway. These concurrent mechanisms compromise cancer cell viability while significantly enhancing tumor immunogenicity, positioning BMP-Au as an innovative nanoadjuvant for cancer treatment that leverages both cellular stress mechanisms and immune activation.
研究领域:
肿瘤免疫学
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纳米医学
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生物材料学
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DOI
PubMed
高影响因子
LANGMUIR
·
2026
·
IF 4.4
Qinye Liu,Zhaoxiang Li,Tong Ye,Guifeng Kang,Hui Gan,Yueyue Chen
Chemotherapy with spatiotemporal precision and noninvasiveness offers a new treatment strategy for colorectal cancer. However, this therapy still has shortcomings in how chemotherapeutic drugs are visualized and their antitumor effects. To improve the therapeutic efficacy, we have fabricated a facile host–guest complex (OTC) that resorts to noncovalent interactions among oxaliplatin (OxPt), photosensitizer (TTVP), and cucurbit[8]uril (CB[8]). OTC significantly enhanced the aggregation-induced emission (AIE) effect of TTVP. We further confirmed that OTC targeted aggregation in tumors by xenograft nude mouse models. This enabled the functions of tracing the chemotherapeutic drug, localizing the tumor, and targeting tumor accumulation. The tumor growth inhibition value (TGI) was 68.01% in the OTC group. Importantly, OTC-regulated drug release was observed through spermidine exchange in vitro and in vivo. The toxicity of OTC to normal cells under light-avoidance conditions was significantly less than that of conventional chemotherapeutic agents (OxPt), implying that OTC exhibited high efficacy and low toxicity. Upon light irradiation, OTC generated reactive oxygen species (ROS), leading to oxidative damage, while MDA levels were elevated, but SOD and CAT activities were reduced. We found that HMGB1, CRT, and ATP in the OTC-treated group increased by 87.20, 43.30, and 34.60% in vitro, respectively, compared with the control group. Transcriptomic analysis revealed upregulation of pathways related to immune activation, suggesting that OTC treatment primed the tumor for immunotherapy. The possible biological mechanism behind this was that OTC activated oxidative damage to induce immunogenic cell death (ICD). Overall, OTC offers a simple, visual, and highly efficient method for transporting platinum to improve chemotherapy. It also provides a novel strategy for combining chemotherapy and immunotherapy in solid tumors.
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DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Chenqian Feng,Lingfeng Zhou,Bo Chen,Hui Li,Min Mu,Rangrang Fan,Haifeng Chen,Gang Guo
Melanoma, a common malignant skin tumor, faces challenges with multidrug resistance and high recurrence rates. Combining photodynamic therapy (PDT) and immunotherapy offers a promising personalized treatment approach. However, poor water solubility and significant side effects of photosensitizers and immune checkpoint inhibitors (ICIs) limit their application. Enhancing delivery efficiency while reducing adverse effects is crucial. Herein, we formulate BM@HSSC nanoparticles (NPs), which consist of a reduction-responsive hyaluronic acid (HA) backbone modified with photosensitizer Chlorin e6 (Ce6) and loaded with the programmed cell death-ligand 1 (PD-L1) inhibitor BMS-1. This system synergistically integrates PDT, immunogenic cell death (ICD), and immunotherapy for melanoma treatment. BM@HSSC NPs target and accumulate at the tumor site via the CD44 receptor. The disulfide bonds in the nanoparticles react with high GSH concentrations in tumor cells, rapidly releasing Ce6 and BMS-1. Under 660 nm laser irradiation, BM@HSSC NPs generate cytotoxic reactive oxygen species (ROS), inducing cell apoptosis and triggering ICD via. PDT Damage-associated molecular patterns (DAMPs) and tumor-associated antigens (TAAs) released from ICD promote dendritic cell (DC) maturation, enhancing antigen presentation and activating cytotoxic T lymphocytes (CTLs). Meanwhile, BMS-1 blocks the programmed cell death-1 (PD-1)/PD-L1 pathway, countering the immunosuppressive tumor microenvironment and inhibiting tumor cell immune escape. This strategy amplifies antitumor immune responses by enhancing immunogenicity and synergizing with ICIs, resulting in robust antitumor efficacy.
研究领域:
肿瘤学
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纳米医学
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免疫学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2023
·Vol. 27
·期 1
·108702-108702
·
IF 5.8
Hong-Yang Zhao,Kun-Heng Li,Dan-Dan Wang,Zhi-Li Zhang,Zi-Jian Xu,Ming-Hui Qi,Shi-Wen Huang
Immunogenic cell death (ICD) can activate the anticancer immune response and its occurrence requires high reliance on oxidative stress. Inducing mitochondrial reactive oxygen species (ROS) is a desirable capability for ICD inducers. However, in the category of ICD-associated drugs, numerous reported ICD inducers are a series of anthracyclines and weak in ICD induction. Herein, a mitochondria-targeting dihydroartemisinin derivative (T-D) was synthesized by conjugating triphenylphosphonium (TPP) to dihydroartemisinin (DHA). T-D can selectively accumulate in mitochondria to trigger ROS generation, leading to the loss of mitochondrial membrane potential (ΔΨ m ) and ER stress. Notably, T-D exhibits far more potent ICD-inducing properties than its parent compound. In vivo , T-D-treated breast cancer cell vaccine inhibits metastasis to the lungs and tumor growth. These results indicate that T-D is an excellent ROS-based ICD inducer with the specific function of trigging vigorous ROS in mitochondria and sets an example for incorporating artemisinin-based drugs into the ICD field.
研究领域:
肿瘤学
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免疫学
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药理学
·
细胞生物学
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DOI
PubMed
高影响因子
Bioactive Materials
·
2023
·
IF 18.9
Yang Yang,Yefei Zhu,Kairuo Wang,Yunqiu Miao,Yuanyuan Zhang,Jie Gao,Huanlong Qin,Yang Zhang
Chemotherapy can induce a robust T cell antitumor immune response by triggering immunogenic cell death (ICD), a process in which tumor cells convert from nonimmunogenic to immunogenic forms. However, the antitumor immune response of ICD remains limited due to the low immunogenicity of tumor cells and the immunosuppressive tumor microenvironment. Although autophagy is involved in activating tumor immunity, the synergistic role of autophagy in ICD remains elusive and challenging. Herein, we report an autophagy amplification strategy using an ion-chelation reaction to augment chemoimmunotherapy in cancer treatments based on zinc ion (Zn 2+ )-doped, disulfiram (DSF)-loaded mesoporous silica nanoparticles ( [email protected] ). Upon pH-sensitive biodegradation of [email protected] , Zn 2+ and DSF are coreleased in the mildly acidic tumor microenvironment, leading to the formation of toxic Zn 2+ chelate through an in situ chelation reaction. Consequently, this chelate not only significantly stimulates cellular apoptosis and generates damage-associated molecular patterns (DAMPs) but also activates autophagy, which mediates the amplified release of DAMPs to enhance ICD. In vivo results demonstrated that [email protected] exhibit strong therapeutic efficacy via in situ ion chelation and possess the ability to activate autophagy, thus enhancing immunotherapy by promoting the infiltration of T cells. This study provides a smart in situ chelation strategy with tumor microenvironment-responsive autophagy amplification to achieve high tumor chemoimmunotherapy efficacy and biosafety.
研究领域:
肿瘤学
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药学
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免疫学
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PubMed
高影响因子
Cancer Nanotechnology
·
2023
·Vol. 14
·期 1
·1-19
·
IF 5.7
Wu Yueyao,Wang Runtian,Shen Peiliang,Zhou Weijia,Chen Chao,Yang Kaiyong,Yang Jingjing,Song Yujun,Han Xin,Guan Xiaoxiang
Cancer treatment by inducing tumor cell immunogenic cell death (ICD) is critical for tumor therapy. However, ICD activation by single pathway is often limited in practical application due to its low efficiency. In addition, the low pH and anoxic microenvironments in solid tumors greatly limit the effective activation of ICD. Herein, hollow manganese dioxide (H-MnO2) nanomaterials were selected to load both Mitoxantrone (MTZ) and Chlorin e6 (Ce6) due to its hollow structure and ability to release drugs in the acidic environments. Thus, the synergy of photodynamic therapy (PDT), photothermal therapy (PTT) and chemotherapy can induce the process of immunogenic cell death, stimulate the maturation of dendritic cells (DCs), and activate the immune response to kill tumor cells dramatically. Efficient immunotherapeutic effects were obtained when MnO2-C/M-HA was given intravenously to 4T1 tumor-bearing BALB/c mice with 660 nm near-infrared laser irradiation. This study overcame the limitations of monotherapy and provided a multifunctional platform for tumor immunotherapy.
研究领域:
癌症治疗
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纳米技术
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免疫学
·
药物递送系统
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产品关联
DOI
高影响因子
ACS Nano
·
2025
·
IF 16
Si-Min Zeng,Wen-Qiang Qu,Yu-Liang Sun,Ke-Wei Chen,Kai Zhao,Jian-Hua Yan,Cheng Zhang,Chun-Xiao Liang,Yu Chen,Ting Pan,Aixi Yu,Xian-Zheng Zhang
Hypoxia-related adenosine (Ado) exerts an immunosuppressive effect in tumors by binding to the metabolic checkpoint Ado A2A receptors (A2AR), thereby hindering the activation of antitumor immunity induced by immunogenic cell death (ICD). In this study, a MnO2-assisted photosynthetic bacteria (PSB) biohybrid (MnO2@PSB) is developed to enhance tumor photothermal immunotherapy by interfering with the Ado-A2AR metabolic pathway. Specifically, manganese dioxide (MnO2) nanoflowers are conjugated onto PSB by the carbodiimide reaction to construct the biohybrid MnO2@PSB. As a photothermal agent, MnO2@PSB generates heat to “burn” tumor cells under 808 nm laser irradiation, inducing tumor cell ICD. Meanwhile, MnO2@PSB catalyzes the decomposition of endogenous hydrogen peroxide into oxygen to alleviate tumor hypoxia, thereby reducing Ado production and downregulating the expression of A2AR, further reversing the tumor immunosuppressive microenvironment and amplifying the ICD effects. In various mouse 4T1 tumor models, MnO2@PSB can enhance antitumor immune responses, prolong mouse survival, and significantly inhibit tumor growth, recurrence, and metastasis under 808 nm laser irradiation. Collectively, this study provides a direction for enhanced antitumor immunotherapy through regulating metabolic pathways.
研究领域:
肿瘤学
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免疫治疗
·
代谢通路调控
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Luoyijun Xie,Li Wang,Ling Li,Chutong Liu,Lihao Guo,Yingying Liao,Shuyi Zhou,Weiwei Wu,Yanhong Duo,Leilei Shi,Miaomiao Yuan
Photosensitizers have been widely used to cause intratumoral generation of reactive oxygen species (ROS) for cancer therapy, but they are easily disturbed by the autophagy pathway, a self-protective mechanism by mitigating oxidative damage. Hereby, we reported a simple and effective strategy to construct a carrier-free nanodrug, Ce6@CQ namely, based on the self-assembly of the photosensitizer chlorin e6 (Ce6) and the autophagy inhibitor chloroquine (CQ). Specifically, Ce6@CQ avoided the unexpected toxicity caused by the regular nanocarrier and also ameliorated its stability in different conditions. Light-activated Ce6 generated cytotoxic ROS and elicited part of the immunogenic cell death (ICD). Moreover, CQ induced autophagy dysfunction, which hindered self-healing in tumor cells and enhanced photodynamic therapy (PDT) to exert a more potent killing effect and more efficient ICD. Also, Ce6@CQ could effectively accumulate in the xenograft breast tumor site in a mouse model through the enhanced permeability and retention (EPR) effect, and the growth of breast tumors was effectively inhibited by Ce6@CQ with light. Such a carrier-free nanodrug provided a new strategy to improve the efficacy of PDT via the suppression of autophagy to digest ROS-induced toxic substances.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
免疫治疗
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Qingyu Zong,Jisi Li,Xuan Xiao,Xiaojiao Du,Youyong Yuan
The selective activation of stimuli-responsive polymers in the tumor microenvironment is a great concern to achieve intelligent cancer therapy, but most of them show inadequate response due to insufficient endogenous triggering agents. Herein, we rationally designed a reactive oxygen species (ROS)-responsive cinnamaldehyde (CA)-based poly(thioacetal), consisting of ROS-responsive thioacetal (TA) and ROS-generating agent CA, with self-amplified chain-shattering polymer degradation . The mechanism of self-amplified chain-shattering is that endogenous ROS as a triggering agent facilitates chain cleavage of TA with the release of CA, which in turn produces more ROS through mitochondrial dysfunction, resulting in an exponential polymer degradation cascade. The polymer can be further modified with anticancer drug doxorubicin (DOX) for cooperative amplification of oxidative stress and immunogenic cell death (ICD) of tumor cells, thereby boosting the effect of chemo-immunotherapy. The self-amplified chain-shattering polymer designed in this work holds great promise in developing stimuli-responsive polymers for efficient drug delivery. Statement of significance This study presented an approach to utilize self-amplified chain-shattering cinnamaldehyde-based poly (thioacetal) as a drug delivery system to restrain tumor growth and boost chemo-immunotherapy. The endogenous ROS as a triggering agent initiates the chain cleavage with the release of CA, which in turn produces ROS through mitochondria dysfunction, resulting in an exponential polymer degradation cascade and rapid drug release.
研究领域:
癌症治疗
·
高分子科学
·
药物递送系统
·
生物医学工程
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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）