Science Advances
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2024
·Vol. 10
·期 6
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IF 11.7
Zhanzhan Zhang,Zheng Pan,Qiushi Li,Qingqing Huang,Linqi Shi,Yang Liu
Nanoparticle-based cancer immunotherapy has shown promising therapeutic potential in clinical settings. However, current research mainly uses nanoparticles as delivery vehicles but overlooks their potential to directly modulate immune responses. Inspired by the endogenous endoplasmic reticulum (ER) stress caused by unfolded/misfolded proteins, we present a rationally designed immunogenic cell death (ICD) inducer named NanoICD, which is a nanoparticle engineered for ER targeting and retention. By carefully controlling surface composition and properties, we have obtained NanoICD that can effectively accumulate in the ER, induce ER stress, and activate ICD-associated immune responses. In addition, NanoICD is generally applicable to various proteins and enzymes to further enhance the immunomodulatory capacity, exemplified by encapsulating catalase (CAT) to obtain NanoICD/CAT, effectively alleviated immunosuppressive tumor microenvironment and induced robust antitumor immune responses in 4T1-bearing mice. This work demonstrates engineered nanostructures’ potential to autonomously regulate biological processes and provides insights into the development of advanced nanomedicines for cancer treatment.
研究领域:
纳米技术
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癌症生物学
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免疫学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2024
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IF 18
Xiaoxiao Hu,Mo Zhang,Cuilu Quan,Saisai Ren,Wei Chen,Jing Wang
Immunogenic cell death (ICD) represents a modality of apoptosis distinguished by the emanation of an array of damage-related molecular signals. This mechanism introduces a novel concept in the field of contemporary tumor immunotherapy. The inception of reactive oxygen species (ROS) within tumor cells stands as the essential prerequisite and foundation for ICD induction. The formulation of highly efficacious photodynamic therapy (PDT) nanomedicines for the successful induction of ICD is an area of significant scientific inquiry. In this work, we devised a ROS-responsive and triple-synergistic mitochondria-targeted polymer micelle (CAT/CPT-TPP/PEG-Ce6, CTC) that operates with multistage amplification of ROS to achieve the potent induction of ICD. Utilizing an “all-in-one” strategy, we direct both the PDT and chemotherapeutic units to the mitochondria. Concurrently, a multistage cyclical amplification that caused by triple synergy strategy stimulates continuous, stable, and adequate ROS generation (domino effect) within the mitochondria of cells. Conclusively, influenced by ROS, tumor cell-induced ICD is effectively activated, remodeling immunogenicity, and enhancing the therapeutic impact of PDT when synergized with chemotherapy. Empirical evidence from in vitro study substantiates that CTC micelles can efficiently provoke ICD, catalyzing CRT translocation, the liberation of HMGB1 and ATP. Furthermore, animal trials corroborate that polymer micelles, following tail vein injection, can induce ICD, accumulate effectively within tumor tissues, and markedly inhibit tumor growth subsequent to laser irradiation. Finally, transcriptome analysis was carried out to evaluate the changes in tumor genome induced by CTC micelles. This work demonstrates a novel strategy to improve combination immunotherapy using nanotechnology.
研究领域:
癌症治疗
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纳米技术
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免疫疗法
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药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
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2025
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IF 3.9
Yuan Li,Haolong Qi,Yingjie Geng,Jianguo Gao,Xiaoqing Cai
The combination therapy strategy exerts a significant anti-tumour effect by synergistically eliminating tumour cells through the use of two or more treatments. Nanomedicine delivery systems are widely employed in cancer therapy owing to their ability to effectively improve drug solubility and enhance drug targeting. To this end, we have designed and developed a nano-targeted drug delivery platform PAE–PEG–ss–Ce6/DOX nanoparticles (PPCD NPs), for the co-delivery of the photosensitiser chlorin e6 (Ce6) and the chemotherapeutic agent doxorubicin (DOX). The nanoparticles exhibit a mean particle size of 128.74 ± 0.80 nm, demonstrating excellent serum stability and pH/glutathione (GSH)-responsive release characteristics in vitro. Compared to monotherapy, PPCD NPs exhibited enhanced cytotoxicity and cellular uptake, effectively inhibiting cell proliferation by inducing reactive oxygen species (ROS) production. The results of the immunogenic cell death (ICD) experiments demonstrated that PPCD NPs induced a robust ICD effect through the synergistic action of DOX and Ce6, thereby activating anti-tumour immunity and achieving combination therapy. In vivo experiments and histopathological analysis demonstrated that PPCD NPs exhibit excellent tumour targeting, high anti-tumour efficacy and low biotoxicity. These findings demonstrated the superiority of the phototherapy–chemotherapy–immunotherapy synergistic treatment strategy and indicate that PPCD NPs hold promise as a safe and effective anti-tumour nanoscale targeted drug delivery system.
研究领域:
纳米医学
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癌症治疗
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药物递送系统
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免疫治疗
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生物化学
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药理学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Jingru Cui,Zhonghui Xue,Zhengxian Zhang,Huanhuan Zhu,Mingsan Miao,Yagang Song,Xiaofang Li,Huahui Zeng,Xiangxiang Wu
Chemodynamic therapy (CDT) is currently constrained by insufficient endogenous H 2 O 2 , enhanced antioxidant defense, weakly acidic conditions in pancreatic cancer. However, the CDT's immunotherapeutic potential hinges on radical-mediated immunogenic cell death (ICD) induction, motivating development of potent self-cascading radical nanogenerators. Herein, this work engineers carrier-free nanoparticles (IAA NPs) through metal-organic self-assembly of Fe 3+ , artesunate (AS) and PD-L1 antibody (αPD-L1), exhibiting high drug loading (AS: 80.62%, Fe 3+ : 4.57%, and αPD-L1: 14.81%), excellent stability and GSH/pH-dependent drug release. IAA NPs achieve GSH-triggered Fe 3+ reduction to Fe 2+ , catalyzing AS decomposition into carbon-centered radicals, with this radicalogenesis being H 2 O 2 /pH-independent while concurrently depleting intratumoral GSH antioxidant. These free radicals effectively induce ICD via apoptosis pathway, eliciting CRT exposure, HMGB1/ATP release, and efficient DC maturation. In Pan02 tumor-bearing mice, IAA NPs efficiently triggers ICD, promoting DC maturation, intratumoral CD4 + /CD8 + T-cell infiltration, and markedly inhibiting tumor growth. Concurrently, αPD-L1 blocks PD-1/PD-L1 pathway and restores T cell recognition, thereby enhancing the antitumor immune response. In addition, the favorable pharmacokinetic profiles, coupled with inherent biocompatibility and biosafety, collectively enhance IAA NPs’ translational potential. Basically, IAA NPs represent a novel strategy to improve combination chemodynamic-immunotherapy through radical-induced ICD and PD-L1 blockade.
研究领域:
纳米医学
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癌症免疫治疗
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化学动力学治疗
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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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免疫学
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Ping Sun,Li Huang,Zimu Li,Yao Yang,Shiman Lu,Nansha Gao,Hongzhong Chen,Xiaowei Zeng,Zhongjian Xie
Ferroptosis is a form of regulated cell death (RCD) induced by excessive lipid peroxidation, representing a promising mechanism for suppressing tumors. Herein, a type of nanoplatform (ODLP-PEGH8) was developed to harness the power of ferroptosis and immunogenic cell death (ICD) for the treatment of breast cancer. To enhance its effectiveness, this project incorporated a pH-responsive PEGH8 peptide onto the surface of the nanoplatform. This modification not only promoted charge reversal within the tumor microenvironment but also improved the cellular uptake efficiency of the nano-system, facilitating intracellular lysosomal escape. Subsequently, ODLP-PEGH8 rapidly degraded under conditions of low pH and exposure to light, resulting in the sequential release of the ferroptosis inducer lapatinib (LTB) and oxaliplatin (OXA). LTB induced ferroptosis and exhibited potent tumor cell-killing effects, while the ODLP-PEGH8, which possessed photothermal properties, worked with OXA to effectively induce ICD within the tumor. This dual approach triggered anti-tumor immune responses and had a substantial impact on tumor immunotherapy. All the results confirm that ODLP-PEGH8 mediates ferroptosis, enhancing the proliferation and infiltration of cytotoxic lymphocytes (CLTs) while demonstrating excellent biological safety in vivo. These findings suggest a promising therapeutic strategy for targeting ferroptosis in cancer treatment.
研究领域:
肿瘤学
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生物材料学
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免疫治疗
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2022
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IF 11.467
Qian Chen,Shuai Zhou,Yuan Ding,Dali Chen,Naseer Sintali Dahiru,Hailei Tang,Hui Xu,Meng Ji,Xueyi Wang,Zixuan Li,Qinying Chen,Yanan Li,Jiasheng Tu,Chunmeng Sun
Tumor recurrence and metastasis after surgery remain challenges for tumor treatment. Strategy that can promote the immunogenicity , activate adaptative immune response and eliminate post-operative immunosuppression would be a promising way to achieve a desired clinical benefit. In this study, immunogenic cell death (ICD) priming anti-tumor adaptive immune response was executed to potentiate immune checkpoint blockade (ICB) therapy through the PD1/PDL1 pathway for postsurgical treatment. Here, we present a bio-responsive and cargo-catchable gel depot composed of pullulan and chitosan cross-linking through matrix metalloproteinase (MMP) sensitive peptide for co-delivery of anti-programmed death-ligand 1 antibody (aPDL1) and doxorubicin -encapsulated liposomes (DOX-Lip). This drug carrier showed expected ability to respond to the highly expressed MMP in postsurgical tumor microenvironment (TME). In vivo studies on 4T1 breast tumor mouse model demonstrated that the gel depot could efficiently prolong the mouse survival after tumor resection by preventing tumor recurrence and metastasis. The results suggested that ICD combining with PD1/PDL1 blockade based on the bio-responsive and cargo-catchable gel depot could facilitate the maturation of DCs and reverse the immunosuppressive environment in tumor resection area, thus amplifying the systemic anti-tumor immune response.
研究领域:
癌症治疗
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免疫学
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生物医学工程
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药学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Siqi Geng,Baoru Fang,Ke Wang,Fang Wang,Yiqing Zhou,Yike Hou,M. Zubair Iqbal,Yanping Chen,Zhangsen Yu
Photothermal therapy (PTT) is a promising technology that can achieve the thermal ablation of tumors and induce immunogenic cell death (ICD). However, relying solely on the antitumor immune responses caused by PTT-induced ICD is insufficient to suppress tumor metastasis and recurrence effectively. Fortunately, multifunctional nanoformulation-based synergistic photothermal immunotherapy can eliminate primary and metastatic tumors and inhibit tumor recurrence for a long time. Herein, we select polydopamine (PDA) nanoparticles to serve as the carrier for our nanomedicine as well as a potent photothermal agent and modulator of macrophage polarization. PDA nanoparticles are loaded with the insoluble immune adjuvant Imiquimod (R837) to construct PDA(R837) nanoformulations. These straightforward yet highly effective nanoformulations demonstrate excellent performance, allowing for successful triple-negative breast cancer (TNBC) treatment through synergistic photothermal immunotherapy. Moreover, experimental results showed that PDA(R837) implementation of PTT is effective in the thermal ablation of primary tumors while causing ICD and releasing R837, further promoting dendritic cell (DC) maturation and activating the systemic antitumor immune response. Furthermore, PDA(R837) nanoformulations inhibit tumor metastasis and recurrence and achieve M1 phenotype macrophage polarization, achieving long-term and excellent antitumor efficacy. Therefore, the structurally simple PDA(R837) nanoformulations provide cancer treatment and have excellent clinical translational application prospects.
研究领域:
纳米技术
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癌症研究
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免疫治疗
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生物医学工程
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药学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
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IF 4.8
Mengxue Zhou,Ying Wang,Hongchun Cui,Huan Geng,Lifo Ruan,Yanni Zhao,Chuang Zhou,Weidong Dai,Jun Chen,Jizhong Yu,Haipeng Lv,Zhi Lin
Enhancing cancer immunotherapy using methods that induce immunogenic cell death (ICD) can significantly improve its effectiveness and profoundly influence its role as a highly efficient cancer treatment strategy. However, the limited penetration of cytotoxic T cells into tumors, owing to dense tumor fibrosis, remains a significant barrier to immunotherapy. A tumor microenvironment-sensitive intelligent dual-drug delivery system was developed to simultaneously deliver epigallocatechin-3-gallate (EGCG) and doxorubicin (DOX) to mitochondria. EGCG enhanced the mitochondria-targeted action of DOX and increased damage to the mitochondrial electron transport chain which facilitated capturing electrons in the mitochondrial matrix of DOX. Subsequently, DOX molecules form a semiquinone intermediate and electrons are transferred to oxygen to generate reactive oxygen species (ROS) that induce mitochondrial apoptosis. These results indicate that EGCG amplifies the combined effects of chemo/chemodynamic therapy of DOX, demonstrating a pronounced synergistic ICD effect that recruits CD8+ T cells to the tumor microenvironment (TME). In addition, EGCG promotes T-cell infiltration into tumor tissues by inhibiting the transforming growth factor-β signaling pathway, thereby significantly enhancing antitumor efficacy. This study advances the efficacy of immunotherapy through bidirectional synergy, which not only enhances intrinsic tumor immunogenicity but also overcomes the extrinsic physical barriers of tumors, providing a new direction for the development of broadly applicable immunotherapies.
研究领域:
肿瘤学
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药理学
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生物医学工程
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Liu Ding,Huang Huilin,Zhao Bingxia,Guo Weihong
Melanin, as a natural product, has been used as an extraordinary ingredient for nanomedicine due to its great biocompatibility and light responsive property. In this study, polydopamine (PDA), an analog of melanin, was extracted from dopamine and encapsulated with doxorubicin (DOX). The as-prepared nanoparticles (NPs) with good stability, great biosafety and high near infrared (NIR) responsive property ameliorated the cell uptake of DOX in OS-RC-2/ADR cells, exhibited synergistic chemo/photothermal (PTT)/photodynamic (PDT) effects, induced the release of damage associated molecular patterns (DAMPs), and finally, led to immunogenic cell death (ICD). In general, it was suggested that PDA-DOX NPs with NIR irradiation could serve as a promising agent for tumor therapy.
研究领域:
纳米技术
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肿瘤学
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药学
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生物医学工程
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DOI
PubMed
高影响因子
Theranostics
·
2021
·
IF 11.556
Junjie Ren,Jing Zhou,Han Liu,Xiaodan Jiao,Yang Cao,Zhigang Xu,Yuejun Kang,Peng Xue
Introduction: An imbalance in redox homeostasis consistently inhibits tumor cell proliferation and further causes tumor regression. Thus, synchronous glutaminolysis inhibition and intracellular reactive oxygen (ROS) accumulation cause severe redox dyshomeostasis, which may potentially become a new therapeutic strategy to effectively combat cancer. Methods: Mitochondrial-targeting liposomal nanoparticles (abbreviated MLipRIR NPs) are synthesized by the encapsulation of R162 (inhibitor of glutamate dehydrogenase 1 [GDH1]) and IR780 (a hydrophobic sonosensitizer) within the lipid bilayer, which are exploited for ultrasound (US)-activated tumor dyshomeostasis therapy reinforced by immunogenic cell death (ICD). Results: R162 released from MLipRIR NPs disrupts the glutaminolysis pathway in mitochondria, resulting in downregulated enzymatic activity of glutathione peroxidase (GPx). In addition, loaded IR780 can generate high levels of ROS under US irradiation, which not only interrupts mitochondrial respiration to induce apoptosis but also consumes local glutathione (GSH). GSH depletion accompanied by GPx deactivation causes severe ferroptosis of tumor cells through the accumulation of lipid peroxides. Such intracellular redox dyshomeostasis effectively triggers immunogenic cell death (ICD), which can activate antitumor immunity for the suppression of both primary and distant tumors with the aid of immune checkpoint blockade. Conclusions: Taking advantage of multimodal imaging for therapy guidance, this nanoplatform may potentiate systemic tumor eradication with high certainty. Taken together, this state-of-the-art paradigm may provide useful insights for cancer management by disrupting redox homeostasis.
研究领域:
肿瘤学
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纳米技术
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免疫治疗
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Shengming Wu,Huawei Liu,Han Zhou,Jingwen Qin,Chenlong He,Ming Yin,Hongyi Zhang,Shan Hua,Zhonghua Liu,Yilong Wang
Dual-protein co-delivery nanocarriers enabling full-course ICD through to antigen presentation • A tumor-targeted nanoplatform (P/A@MnO₂-M) was developed to achieve full-course ICD activation, from tumor-specific ICD induction via PPE to efferocytosis blockade via Annexin A5. This strategy bridges cell death induction, DAMPs release, and antigen presentation, addressing the challenge of transient signals and insufficient presentation in conventional ICD approaches. • Distinct regulation of different phagocytic cell types to block clearance while preserving antigen presentation • This study precisely regulates different phagocytic cell types by selectively blocking PS-dependent immunosilent efferocytosis in macrophages while preserving dendritic cell-mediated uptake through CRT pathways, ensuring efficient antigen presentation and subsequent immune activation. • Enhancement of macrophage antigen-presenting function to bridge ICD to adaptive immunity • Beyond conventional ICD strategies, this platform enhances the antigen-presenting capacity of macrophages, enabling effective antigen delivery to dendritic cells and T cells, bridging innate sensing with adaptive immune activation, and addressing the overlooked role of macrophages in ICD-based immunity. • Integration with immune checkpoint blockade to overcome immune inertia in cold tumors • By prolonging DAMPs exposure and remodeling the tumor microenvironment, P/A@MnO₂-M enhances responsiveness to αPD-L1 therapy, effectively overcoming immune inertia in cold tumors and demonstrating strong potential for synergistic immunotherapy. Immunogenic cell death (ICD) holds great promise for eliciting antitumor immunity but remains challenged by rapid signal clearance, insufficient antigen presentation, and dominant immunosuppression within the tumor microenvironment. Here, we report a sequential immune activation strategy through precise killing and phagocytosis regulation based on a porous MnO 2 -based nanoplatform (P/A@MnO 2 -M) integrating tumor-specific ICD induction with efferocytosis blockade for addressing transient ICD signals and immune tolerance. This nanotherapeutics prolongs danger signal exposure, prolonged immunogenic signaling, and strengthens immune activation upon a tumor membraned encapsulated carrier with co-delivery of PPE, a histone H1-targeting protease, and Annexin A5 (ANXA5), a PS-binding protein. Notably, it reprograms macrophages toward enhanced antigen presentation, facilitates dendritic cell activation and CD8 + T cell infiltration, completing the full ICD process from induction to adaptive immunity. In-vivo studies also confirm the synergistic anti-tumor effects of comprehensive tumor microenvironment remodeling and enhanced αPD-L1 efficacy, which offers a promising avenue for cancer immunotherapy. A tumor membrane-coated nanoplatform (P/A@MnO 2 -M) enables co-delivery of two functional proteins to induce ICD and suppress efferocytosis. This strategy ensures precise tumor killing, prolongs danger signal exposure, avoids immune cell damage, and preserves antigen-presenting processes. By supporting sustained DAMPs release and CD8 + T cell activation, it achieves full-course immune activation to remodel the immunosuppressive microenvironment in cold tumors. Download: Download high-res image (196KB) Download: Download full-size image
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DOI
高影响因子
Interdisciplinary Medicine
·
2025
·
IF 13.6
Liping Yang,Fangli Liao,Yanran Tong,Tong Huang,Yan-e Du,Siyang Wen,Linshan Jiang,Lanlang Peng,Hua Sun,Gaoli Zhang,Weixian Chen
Cancer stem cells exhibit flexible metabolic profiles. However, the underlying mechanisms for differential metabolic pathways affecting stemness maintenance in gastric cancer are poorly understood. Here, we reveal the role of serine hydroxymethyltransferase-2 (SHMT2)/serine-mediated crosstalk between one-carbon metabolism and lipid metabolism in the stemness maintenance of gastric cancer. Clinically, SHMT2 was significantly highly expressed in Gastric cancer cells (GCs) and gastric cancer stem cells, and was associated with clinical malignant features and poor prognosis in gastric cancer patients. Mechanistically, inhibition of SHMT2 expression resulted in diminished serine levels in one-carbon metabolism, which subsequently modified the composition and fluidity of membrane phospholipids, leading to a reduction in lipid rafts within cellular membranes. The remodeling of membrane phospholipids hindered the localization of γ-secretase to lipid rafts, thereby inhibiting the cleavage of CD44 and the subsequent production of CD44-ICD. Consequently, the transcriptional regulation of c-Myc and KLF4 by CD44-ICD was reduced, ultimately disrupting the maintenance of stemness in gastric cancer cells. Together, these results provide compelling evidence for the metabolic adaptability of cancer stem cells, and the SHMT2/serine/lipid rafts signaling axis holds promise as a potential biomarker for the diagnosis and prognosis of gastric cancer. Furthermore, we synthesized HA-Exo-si SHMT2 to investigate targeted therapy for GC, offering a novel approach for the clinical treatment of gastric cancer.
研究领域:
生物化学
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分子生物学
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肿瘤学
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产品关联
DOI
高影响因子
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