Pub Date : 2025-03-19DOI: 10.1016/j.nantod.2025.102717
Jingyou Bi , Yuchen Han , Xinli Han , Yanan Wu , Song Liao , Yinglong Zhang , Xiaolu Han , Zengming Wang , Jianxiong Li , Aiping Zheng , Wenzhi Bi
Low delivery efficiency and accompanying systematic toxicity of therapeutic agents have affected the efficacy of chemotherapy for osteosarcoma (OS). Meanwhile, the chemotherapy based on cisplatin, as the single modality, has reached the limits. Here, we designed a liposome nanotheranostic platform that combined cisplatin with decitabine to simultaneously activate the pyroptosis and immunogenic cell death in an effective delivery manner. Specifically, we prepared the targeted liposomal therapeutics (NPCD@ALN). NPCD@ALN effectively accumulated at the bone lesion induced by OS in vivo. Meanwhile, NPCD@ALN released NPCD and ALN when reaching the acidic tumor microenvironment, thus the charge reversing from negative to positive and enabling the better endocytosis of NPCD. NPCD activated caspase-3 to cleave GSDME into pore-forming GSDME-N terminal, letting the cancer cell release pro-inflammatory factors into the extracellular microenvironment. Subsequently, the released inflammatory cytokines promoted the maturation of antigen-presenting cells, the infiltration of cytotoxic T cells and the remodeling of immunosuppressive microenvironment. Eventually, NPCD triggered pyroptosis and immunogenic cell death and evoked the adaptive immune response to realize the powerful synergistic chemotherapy and immunotherapy for osteosarcoma. To summarize, this study exemplified rational therapeutics which facilitated the activation of pyroptosis and antitumor immune response by targeted liposomal cisplatin, and provided innovative combined-therapeutic strategies for osteosarcoma.
{"title":"Activation of pyroptosis and immunogenic cell death by targeted liposomal cisplatin for enhanced chemo-immunotherapy for osteosarcoma","authors":"Jingyou Bi , Yuchen Han , Xinli Han , Yanan Wu , Song Liao , Yinglong Zhang , Xiaolu Han , Zengming Wang , Jianxiong Li , Aiping Zheng , Wenzhi Bi","doi":"10.1016/j.nantod.2025.102717","DOIUrl":"10.1016/j.nantod.2025.102717","url":null,"abstract":"<div><div>Low delivery efficiency and accompanying systematic toxicity of therapeutic agents have affected the efficacy of chemotherapy for osteosarcoma (OS). Meanwhile, the chemotherapy based on cisplatin, as the single modality, has reached the limits. Here, we designed a liposome nanotheranostic platform that combined cisplatin with decitabine to simultaneously activate the pyroptosis and immunogenic cell death in an effective delivery manner. Specifically, we prepared the targeted liposomal therapeutics (NPCD@ALN). NPCD@ALN effectively accumulated at the bone lesion induced by OS <em>in vivo</em>. Meanwhile, NPCD@ALN released NPCD and ALN when reaching the acidic tumor microenvironment, thus the charge reversing from negative to positive and enabling the better endocytosis of NPCD. NPCD activated caspase-3 to cleave GSDME into pore-forming GSDME-N terminal, letting the cancer cell release pro-inflammatory factors into the extracellular microenvironment. Subsequently, the released inflammatory cytokines promoted the maturation of antigen-presenting cells, the infiltration of cytotoxic T cells and the remodeling of immunosuppressive microenvironment. Eventually, NPCD triggered pyroptosis and immunogenic cell death and evoked the adaptive immune response to realize the powerful synergistic chemotherapy and immunotherapy for osteosarcoma. To summarize, this study exemplified rational therapeutics which facilitated the activation of pyroptosis and antitumor immune response by targeted liposomal cisplatin, and provided innovative combined-therapeutic strategies for osteosarcoma.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102717"},"PeriodicalIF":13.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143654583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-19DOI: 10.1016/j.nantod.2025.102711
Xiwei Wang , Zenglin Yin , Nan Liu , Hui Zhang , Zengming Wang , Jinjing Che , Jianchun Li , Aiping Zheng
Natural toxins pose a substantial threat to human health worldwide, with millions of individuals suffering from toxin poisoning annually. Rapid detection and efficient neutralization of these toxins are crucial to ensure human health. Nanobodies (Nbs) are a unique antibody type comprising only variable region fragments of the heavy chain. With properties such as small size, high stability, superior tissue penetration, and ease of production and modification, making Nbs are particularly advantageous in the diagnosis and treatment of natural toxin poisoning. This review outlines the current advancements in the modification of Nbs and highlights the research progress in addressing the diagnosis and treatment of poisoning caused by certain natural toxins. It underscores the potential of Nbs in this field, while also examining their benefits and associated challenges. By doing so, the study lays a robust groundwork for the future application of Nbs in combating natural toxin poisoning. Nbs could play an increasingly important role in diagnosing and treating natural toxin poisoning, contributing to the development of precision medicine.
{"title":"Research progress on nanobodies in the diagnosis and treatment of natural toxin poisoning","authors":"Xiwei Wang , Zenglin Yin , Nan Liu , Hui Zhang , Zengming Wang , Jinjing Che , Jianchun Li , Aiping Zheng","doi":"10.1016/j.nantod.2025.102711","DOIUrl":"10.1016/j.nantod.2025.102711","url":null,"abstract":"<div><div>Natural toxins pose a substantial threat to human health worldwide, with millions of individuals suffering from toxin poisoning annually. Rapid detection and efficient neutralization of these toxins are crucial to ensure human health. Nanobodies (Nbs) are a unique antibody type comprising only variable region fragments of the heavy chain. With properties such as small size, high stability, superior tissue penetration, and ease of production and modification, making Nbs are particularly advantageous in the diagnosis and treatment of natural toxin poisoning. This review outlines the current advancements in the modification of Nbs and highlights the research progress in addressing the diagnosis and treatment of poisoning caused by certain natural toxins. It underscores the potential of Nbs in this field, while also examining their benefits and associated challenges. By doing so, the study lays a robust groundwork for the future application of Nbs in combating natural toxin poisoning. Nbs could play an increasingly important role in diagnosing and treating natural toxin poisoning, contributing to the development of precision medicine.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102711"},"PeriodicalIF":13.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143654584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-18DOI: 10.1016/j.nantod.2025.102708
Qi Liang , Yunbo Luo , Jiao Zeng , Shiqi Han , Yali Wang , Xiaohan Su , Xue Li , Tingting Liang , Jun Liu , Peng Qu , Jiao Shi , Jinsui Li , Cui Ma , Kaijiong Zhang , Shishan Deng , Dongsheng Wang , Panke Cheng , Lingmi Hou
Like other tumors, triple-negative breast cancer (TNBC) exhibits immune evasion characteristics, but the activation of an appropriate immune cascade can effectively suppress TNBC progression. This article focuses on enhancing the cytotoxicity of CD8 T cells as an entry point. In TNBC patients and immunodeficient mouse models, it was found that the proportions of specific CD95hiGL7hiB (acB), CD44hiCD69hiCD4 T (acCD4 T), CD44hiICOShiPSGL1loPD1hi CXCR5hiBCL6hiTfh (acTfh), and PD1hiGranzyme BhiCD8 T (acCD8 T) cells are negatively correlated with tumor progression. Based on the pathological features of localized hypoxia and high lysyl hydroxylase 2(LH2) expression in TNBC, and utilizing the oxygen concentration responsiveness of nitroimidazoles, the homing targeting of cell-derived vesicles, the proteolytic activity of LH2 enzyme on substrate peptides, and the targeted inhibitory effect of nucleic acid aptamers, based on a temporal response strategy, this article designs a composite system of acTfh and primary TNBC cells derived vesicles, interferon gamma (INF-γ) aptamer, hyaluronic acid and polyethyleneimine. This system encapsulates co-stimulatory antigens for acB, acCD4 T, and acCD8 T cells, along with an interleukin 21 (IL21) overexpression plasmid. It can sequentially respond to hypoxia, LH2 enzyme, and IFNγ in TNBC tissues, thereby targeting the promotion of antigen secretion by TNBC cells, activating and expanding acB, acCD4 T, and acCD8 T cells. It activates acB to promote the differentiation of acCD4 T into acTfh cells, inhibits the tumor-promoting escape function of IFNγ produced by acCD4 T cells, targets the promotion of IL21 secretion by acTfh cells, and ultimately activates the cytotoxicity of acCD8 T cells to kill tumor cells. The temporal response strategy of this composite nanosystem offers a potential new approach for the immune treatment of TNBC in the future.
{"title":"Temporal responsive vesicle-INFγ aptamer-PEI/HA system targeted activation of B-CD4T-Tfh-CD8T cells cascade inhibits TNBC progression","authors":"Qi Liang , Yunbo Luo , Jiao Zeng , Shiqi Han , Yali Wang , Xiaohan Su , Xue Li , Tingting Liang , Jun Liu , Peng Qu , Jiao Shi , Jinsui Li , Cui Ma , Kaijiong Zhang , Shishan Deng , Dongsheng Wang , Panke Cheng , Lingmi Hou","doi":"10.1016/j.nantod.2025.102708","DOIUrl":"10.1016/j.nantod.2025.102708","url":null,"abstract":"<div><div>Like other tumors, triple-negative breast cancer (TNBC) exhibits immune evasion characteristics, but the activation of an appropriate immune cascade can effectively suppress TNBC progression. This article focuses on enhancing the cytotoxicity of CD8 T cells as an entry point. In TNBC patients and immunodeficient mouse models, it was found that the proportions of specific CD95<sup>hi</sup>GL7<sup>hi</sup>B (acB), CD44<sup>hi</sup>CD69<sup>hi</sup>CD4 T (acCD4 T), CD44<sup>hi</sup>ICOS<sup>hi</sup>PSGL1<sup>lo</sup>PD1<sup>hi</sup> CXCR5<sup>hi</sup>BCL6<sup>hi</sup>Tfh (acTfh), and PD1<sup>hi</sup>Granzyme B<sup>hi</sup>CD8 T (acCD8 T) cells are negatively correlated with tumor progression. Based on the pathological features of localized hypoxia and high lysyl hydroxylase 2(LH2) expression in TNBC, and utilizing the oxygen concentration responsiveness of nitroimidazoles, the homing targeting of cell-derived vesicles, the proteolytic activity of LH2 enzyme on substrate peptides, and the targeted inhibitory effect of nucleic acid aptamers, based on a temporal response strategy, this article designs a composite system of acTfh and primary TNBC cells derived vesicles, interferon gamma (INF-γ) aptamer, hyaluronic acid and polyethyleneimine. This system encapsulates co-stimulatory antigens for acB, acCD4 T, and acCD8 T cells, along with an interleukin 21 (IL21) overexpression plasmid. It can sequentially respond to hypoxia, LH2 enzyme, and IFNγ in TNBC tissues, thereby targeting the promotion of antigen secretion by TNBC cells, activating and expanding acB, acCD4 T, and acCD8 T cells. It activates acB to promote the differentiation of acCD4 T into acTfh cells, inhibits the tumor-promoting escape function of IFNγ produced by acCD4 T cells, targets the promotion of IL21 secretion by acTfh cells, and ultimately activates the cytotoxicity of acCD8 T cells to kill tumor cells. The temporal response strategy of this composite nanosystem offers a potential new approach for the immune treatment of TNBC in the future.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102708"},"PeriodicalIF":13.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-18DOI: 10.1016/j.nantod.2025.102709
Xiangyu Chu , Dongqi Li , Xiaocui Fang , Fuming Liang , Ping Li , Qing You , Chen Wang , Ling Zhu , Yanlian Yang , Yinmo Yang , Xiaodong Tian
Cancer-associated fibroblasts (CAFs) and immunosuppressive microenvironment play important roles in the progression of pancreatic ductal adenocarcinoma (PDAC). Myofibroblast CAFs (myCAFs) and antigen-presenting CAFs (apCAFs) are cancer-promoting fibroblast (CPF) subtypes which could promote dense extracellular matrix (ECM) formation to inhibit drug penetration and induce the immunosuppressive microenvironment. The inhibition of CPF subtypes may help improve the PDAC treatment efficacy. Herein the engineered CPF-inhibiting nanoparticles are constructed with BSA-MnO2-Niclosamide nanoparticles coated with exosomes encapsulating gemcitabine (BMN/GEM@PE) to substantially inhibit the progression and liver metastasis of PDAC by inhibiting the STAT3/p-STAT3 signals. The nanoparticles could significantly reduce the proportion of cancer-promoting CAF subtypes (myCAFs and apCAFs), which induce a shift from immune "cold" tumor to "hot" tumor phenotype. The reduced myCAFs by nanoparticles could promote the drug penetration and the infiltration of CD8+ T cells, and the decreased apCAFs lead to the decrease of the regulatory T cells. The new nanoparticles-based treatment strategies that the CAFs-subtypes modulation may influence the tumor immune microenvironment, which provide an opportunity to improve the immunochemotherapy for PDAC.
{"title":"Immunochemotherapeutic nanoparticles inhibit cancer-promoting fibroblasts subtypes for pancreatic ductal adenocarcinoma","authors":"Xiangyu Chu , Dongqi Li , Xiaocui Fang , Fuming Liang , Ping Li , Qing You , Chen Wang , Ling Zhu , Yanlian Yang , Yinmo Yang , Xiaodong Tian","doi":"10.1016/j.nantod.2025.102709","DOIUrl":"10.1016/j.nantod.2025.102709","url":null,"abstract":"<div><div>Cancer-associated fibroblasts (CAFs) and immunosuppressive microenvironment play important roles in the progression of pancreatic ductal adenocarcinoma (PDAC). Myofibroblast CAFs (myCAFs) and antigen-presenting CAFs (apCAFs) are cancer-promoting fibroblast (CPF) subtypes which could promote dense extracellular matrix (ECM) formation to inhibit drug penetration and induce the immunosuppressive microenvironment. The inhibition of CPF subtypes may help improve the PDAC treatment efficacy. Herein the engineered CPF-inhibiting nanoparticles are constructed with BSA-MnO<sub>2</sub>-Niclosamide nanoparticles coated with exosomes encapsulating gemcitabine (BMN/GEM@PE) to substantially inhibit the progression and liver metastasis of PDAC by inhibiting the STAT3/p-STAT3 signals. The nanoparticles could significantly reduce the proportion of cancer-promoting CAF subtypes (myCAFs and apCAFs), which induce a shift from immune \"cold\" tumor to \"hot\" tumor phenotype. The reduced myCAFs by nanoparticles could promote the drug penetration and the infiltration of CD8<sup>+</sup> T cells, and the decreased apCAFs lead to the decrease of the regulatory T cells. The new nanoparticles-based treatment strategies that the CAFs-subtypes modulation may influence the tumor immune microenvironment, which provide an opportunity to improve the immunochemotherapy for PDAC.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102709"},"PeriodicalIF":13.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natural killer (NK) cell-based immunotherapy represents a promising approach for lung cancer treatment, but its clinical efficacy is limited by poor in vivo persistence and cytotoxicity. Selenium, an essential trace element with immunomodulatory and antitumor properties, offers therapeutic potential, but its application is constrained by low bioavailability. In this study, Chinese Kale (Brassica oleracea var. alboglabra, BOA) was used to construct an oral kale seedlings biotransformation nano-selenium delivery system (Se@BOA). By inducing mitochondrial apoptosis in tumor cells, Se@BOA could effectively reprogram non-small-cell lung cancer immune resistance and enhance the killing abilities of NK cells on A549 cells in vitro, and additionally promote the activation of innate immune cells as well as adoptive NK cells to lyse tumors in vivo. Further mechanistic studies demonstrated that Se@BOA sensitizes tumor cells to NK cells by triggering DNA damage and p53 signaling pathways to induce NKG2DLs and death receptor expression. Additionally, Se@BOA could activate the AHR-STAT3 signaling cascade and promote NKG2D and NKp44 receptor expression on NK cells and thus inhibit tumor immune escape. Taken together, these findings reveal a novel strategy to improve selenium bioavailability and enhance the antitumor efficacy of allogenic human NK cell infusions, potentially informing the development of a plant-derived oral selenium delivery system to support NK cell therapy against lung cancer.
{"title":"Cruciferae-based oral selenium delivery system reprograms antitumor response and enhances the anti-tumor potency of natural killer cells","authors":"Shuoshan Li, Guizhen Li, Kexin Guo, Lin Zhou, Haimei Zhang, Haoqiang Lai, Tianfeng Chen","doi":"10.1016/j.nantod.2025.102713","DOIUrl":"10.1016/j.nantod.2025.102713","url":null,"abstract":"<div><div>Natural killer (NK) cell-based immunotherapy represents a promising approach for lung cancer treatment, but its clinical efficacy is limited by poor <em>in vivo</em> persistence and cytotoxicity. Selenium, an essential trace element with immunomodulatory and antitumor properties, offers therapeutic potential, but its application is constrained by low bioavailability. In this study, Chinese Kale (<em>Brassica oleracea</em> var. <em>alboglabra</em>, <em>BOA</em>) was used to construct an oral kale seedlings biotransformation nano-selenium delivery system (Se@<em>BOA</em>). By inducing mitochondrial apoptosis in tumor cells, Se@<em>BOA</em> could effectively reprogram non-small-cell lung cancer immune resistance and enhance the killing abilities of NK cells on A549 cells <em>in vitro</em>, and additionally promote the activation of innate immune cells as well as adoptive NK cells to lyse tumors <em>in vivo</em>. Further mechanistic studies demonstrated that Se@<em>BOA</em> sensitizes tumor cells to NK cells by triggering DNA damage and p53 signaling pathways to induce NKG2DLs and death receptor expression. Additionally, Se@<em>BOA</em> could activate the AHR-STAT3 signaling cascade and promote NKG2D and NKp44 receptor expression on NK cells and thus inhibit tumor immune escape. Taken together, these findings reveal a novel strategy to improve selenium bioavailability and enhance the antitumor efficacy of allogenic human NK cell infusions, potentially informing the development of a plant-derived oral selenium delivery system to support NK cell therapy against lung cancer.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102713"},"PeriodicalIF":13.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-17DOI: 10.1016/j.nantod.2025.102715
Tian Qiu , Lan Yang , Yupeng Zhu , Jiajia Wang , Ziyi Li , Xinlei Gao , Qi Shen , Jiumeng Zhang , Fengting Lv , Xuli Feng
Simultaneously delivering enzymes and prodrugs to the target sites is an attractive anticancer strategy. In this work, we demonstrate that triskelion lysine containing a tris(triazole)-Cu+ complex (TLTC) can be employed to concurrently load horseradish peroxidase (HRP) and a prodrug (indole-3-acetic acid, IAA) within a single TLTC nanoparticle. This design utilizes Cu+-mediated HRP inhibition to prevent premature activation of IAA, addressing a critical limitation in conventional HRP/IAA systems. Due to the responsion of Cu+ to H2O2, the HRP/IAA system is activated by the high-concentration H2O2 in tumors to generate reactive oxygen species (ROS) for killing tumor cells. The controlled activation of the HRP/IAA system within the tumor microenvironment, mediated by Cu+/H2O2 interaction, represents a significant advancement over conventional enzyme/prodrug therapies. Moreover, the self-supply of H2O2 from the HRP/IAA reaction and the Fenton reaction mediated by Cu+/Cu2+ redox cycling further amplifies the therapeutic effect, creating a self-sustaining cycle of ROS production. This dual mechanism of ROS generation, combining enzyme/prodrug activation and Fenton effect, significantly improves therapeutic outcomes. Thus, our triskelion-based architectures offer the opportunity to activate the enzyme/prodrug therapy (EPT) within the tumor mass while evading systemic toxicity, which represents a promising strategy for developing novel EPT based on triskelion peptide self-assembly.
{"title":"Intracellular in-situ activated enzyme/prodrug strategy based on tris(triazole)-Cu+ complex for cooperative catalytic cancer therapy","authors":"Tian Qiu , Lan Yang , Yupeng Zhu , Jiajia Wang , Ziyi Li , Xinlei Gao , Qi Shen , Jiumeng Zhang , Fengting Lv , Xuli Feng","doi":"10.1016/j.nantod.2025.102715","DOIUrl":"10.1016/j.nantod.2025.102715","url":null,"abstract":"<div><div>Simultaneously delivering enzymes and prodrugs to the target sites is an attractive anticancer strategy. In this work, we demonstrate that triskelion lysine containing a tris(triazole)-Cu<sup>+</sup> complex (TLTC) can be employed to concurrently load horseradish peroxidase (HRP) and a prodrug (indole-3-acetic acid, IAA) within a single TLTC nanoparticle. This design utilizes Cu<sup>+</sup>-mediated HRP inhibition to prevent premature activation of IAA, addressing a critical limitation in conventional HRP/IAA systems. Due to the responsion of Cu<sup>+</sup> to H<sub>2</sub>O<sub>2</sub>, the HRP/IAA system is activated by the high-concentration H<sub>2</sub>O<sub>2</sub> in tumors to generate reactive oxygen species (ROS) for killing tumor cells. The controlled activation of the HRP/IAA system within the tumor microenvironment, mediated by Cu<sup>+</sup>/H<sub>2</sub>O<sub>2</sub> interaction, represents a significant advancement over conventional enzyme/prodrug therapies. Moreover, the self-supply of H<sub>2</sub>O<sub>2</sub> from the HRP/IAA reaction and the Fenton reaction mediated by Cu<sup>+</sup>/Cu<sup>2+</sup> redox cycling further amplifies the therapeutic effect, creating a self-sustaining cycle of ROS production. This dual mechanism of ROS generation, combining enzyme/prodrug activation and Fenton effect, significantly improves therapeutic outcomes. Thus, our triskelion-based architectures offer the opportunity to activate the enzyme/prodrug therapy (EPT) within the tumor mass while evading systemic toxicity, which represents a promising strategy for developing novel EPT based on triskelion peptide self-assembly.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102715"},"PeriodicalIF":13.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-15DOI: 10.1016/j.nantod.2025.102716
Nan Wang , Xiaoyu Fu , Yanan Wu , Lang Yan , Xinyi Zhao , Jinfeng Li , Bijiang Geng , Jiaming Guo , Jikuai Chen
Promoting the maturation of dendritic cells (DCs) play crucial roles in the effectiveness of activating of adaptive immune response. However, the immunosuppressive tumor microenvironments (TME) are thought to impede DC maturation and inhibit antigen presentation, significantly reducing the therapeutic efficacy of immunotherapy. Herein, to realize the cascade activation of DC maturation, we report the first time the integration of reactive oxygen species (ROS)/ferroptosis-mediated immunogenic cell death (ICD) effect, cGAS-STING activation, and tumor-specific delivery of immune adjuvants. To demonstrate this technique, we utilized FDA-approved hollow Prussian Blue (HPB) with good sonodynamic and chemodynamic activities as the template for the self-assembly of Mn-R837. HPB/Mn-R837 not only possesses enhanced US-activated ROS generation capability owing to the construction of heterojunctions, but also exhibits TME-responsive degradation behaviors, achieving the tumor-specific release of Fe2 +, Fe3+, Mn2+, Mn4+, and R837. HPB/Mn-R837-triggered cascade activation of DC maturation were elucidated, including (1) heterojunction fabrication, GSH consumption, and in-situ CDT co-amplified ROS generation as well as ferroptosis could significantly induce robust ICD effect; (2) activation of the cGAS-STING pathway by the released Mn2+ serves to stimulate DC maturation; (3) direct promotion of DC maturation can be achieved by the tumor-specific released R837. As a result, significant antitumor effects have been discovered to completely eradicate primary tumors and effectively inhibit the growth of distant tumors without side effects. This work establishes a novel strategy for the integration of ROS/ferroptosis-induced ICD effect, STING activation, and tumor-specific delivery of immune adjuvants into a single nanostructure for establishing lasting and effective immune responses.
{"title":"Self-assembly Mn-R837 nanosheet sensitized hollow prussian blue for STING activation and ferroptosis co-enhanced sono-immunotherapy","authors":"Nan Wang , Xiaoyu Fu , Yanan Wu , Lang Yan , Xinyi Zhao , Jinfeng Li , Bijiang Geng , Jiaming Guo , Jikuai Chen","doi":"10.1016/j.nantod.2025.102716","DOIUrl":"10.1016/j.nantod.2025.102716","url":null,"abstract":"<div><div>Promoting the maturation of dendritic cells (DCs) play crucial roles in the effectiveness of activating of adaptive immune response. However, the immunosuppressive tumor microenvironments (TME) are thought to impede DC maturation and inhibit antigen presentation, significantly reducing the therapeutic efficacy of immunotherapy. Herein, to realize the cascade activation of DC maturation, we report the first time the integration of reactive oxygen species (ROS)/ferroptosis-mediated immunogenic cell death (ICD) effect, cGAS-STING activation, and tumor-specific delivery of immune adjuvants. To demonstrate this technique, we utilized FDA-approved hollow Prussian Blue (HPB) with good sonodynamic and chemodynamic activities as the template for the self-assembly of Mn-R837. HPB/Mn-R837 not only possesses enhanced US-activated ROS generation capability owing to the construction of heterojunctions, but also exhibits TME-responsive degradation behaviors, achieving the tumor-specific release of Fe<sup>2 +</sup>, Fe<sup>3+</sup>, Mn<sup>2+</sup>, Mn<sup>4+</sup>, and R837. HPB/Mn-R837-triggered cascade activation of DC maturation were elucidated, including (1) heterojunction fabrication, GSH consumption, and in-situ CDT co-amplified ROS generation as well as ferroptosis could significantly induce robust ICD effect; (2) activation of the cGAS-STING pathway by the released Mn<sup>2+</sup> serves to stimulate DC maturation; (3) direct promotion of DC maturation can be achieved by the tumor-specific released R837. As a result, significant antitumor effects have been discovered to completely eradicate primary tumors and effectively inhibit the growth of distant tumors without side effects. This work establishes a novel strategy for the integration of ROS/ferroptosis-induced ICD effect, STING activation, and tumor-specific delivery of immune adjuvants into a single nanostructure for establishing lasting and effective immune responses.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102716"},"PeriodicalIF":13.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-15DOI: 10.1016/j.nantod.2025.102701
Changhong Zhao , Xinshu Zhu , Huili Yang , Fei Kong , Yuxin Yang , Ruohan Gong , Yuqiong Yang , Qinglu Luo , Ruike Zhang , Jieni Fu , Zhenhong Su , Yuan Li , Hongbo Wu
The poor immunogenicity of most tumors caused low efficacy of immunotherapy underlines the importance of activating immune system and provoking immunogenic apoptosis to enhance the treatment efficiency of immunotherapy. Here, the heterojunction was designed against breast cancer through eliciting localized sonodynamic therapy and activating cuproptosis-mediated immunotherapy. The enhanced piezocatalysis effect of Cu2O/vanadium carbide/curcumin (Cu2O/V2C/Cur) mainly originated from the formation of dual interfacial electric field in the heterojunction of Cu2O/V2C under ultrasound irradiation, which can efficiently improve the separation efficiency of electron-hole pairs, inhibit their compounding efficiency, thus enhance the sonodynamic activity. During the process, the apoptosis caused by cuproptosis was also enhanced by down-regulating the expression of downstream cuproptosis-related genes and enhancing the over-accumulation of Cu2 + in mitochondrial respiration-dependent cells through activating JAK-STAT signaling pathway in 4T1 cells. Meanwhile, Cu2O/V2C/Cur also activated immune response by modulating the proportion of CD8+ T cells, which synergizes with sonodynamic-enhanced cuproptosis to efficiently treat breast cancer. Thus, this investigation put up with a feasible method for enhancing the treatment efficiency of immunotherapy by designing a sonodynamic-enhanced cuproptosis strategy.
{"title":"Boosting cuproptosis by activating JAK-STAT signaling pathway and synergrtic with interface-enhanced sonodynamic immunotherapy against cancer","authors":"Changhong Zhao , Xinshu Zhu , Huili Yang , Fei Kong , Yuxin Yang , Ruohan Gong , Yuqiong Yang , Qinglu Luo , Ruike Zhang , Jieni Fu , Zhenhong Su , Yuan Li , Hongbo Wu","doi":"10.1016/j.nantod.2025.102701","DOIUrl":"10.1016/j.nantod.2025.102701","url":null,"abstract":"<div><div>The poor immunogenicity of most tumors caused low efficacy of immunotherapy underlines the importance of activating immune system and provoking immunogenic apoptosis to enhance the treatment efficiency of immunotherapy. Here, the heterojunction was designed against breast cancer through eliciting localized sonodynamic therapy and activating cuproptosis-mediated immunotherapy. The enhanced piezocatalysis effect of Cu<sub>2</sub>O/vanadium carbide/curcumin (Cu<sub>2</sub>O/V<sub>2</sub>C/Cur) mainly originated from the formation of dual interfacial electric field in the heterojunction of Cu<sub>2</sub>O/V<sub>2</sub>C under ultrasound irradiation, which can efficiently improve the separation efficiency of electron-hole pairs, inhibit their compounding efficiency, thus enhance the sonodynamic activity. During the process, the apoptosis caused by cuproptosis was also enhanced by down-regulating the expression of downstream cuproptosis-related genes and enhancing the over-accumulation of Cu<sup>2 +</sup> in mitochondrial respiration-dependent cells through activating JAK-STAT signaling pathway in 4T1 cells. Meanwhile, Cu<sub>2</sub>O/V<sub>2</sub>C/Cur also activated immune response by modulating the proportion of CD8<sup>+</sup> T cells, which synergizes with sonodynamic-enhanced cuproptosis to efficiently treat breast cancer. Thus, this investigation put up with a feasible method for enhancing the treatment efficiency of immunotherapy by designing a sonodynamic-enhanced cuproptosis strategy.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102701"},"PeriodicalIF":13.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-15DOI: 10.1016/j.nantod.2025.102714
Xiaoyu Zhang , Fene Gao , Yizhi Dai , Mingge Wang , Jing Liu
The therapeutic nanomaterials (NMs) are receiving increasing attention for simultaneous diagnostic and therapeutic applications. Bismuth (Bi)-based NMs (Bi NMs) show excellent potential for building therapeutic platforms due to their sensitivity to X-ray, semiconducting properties, and unique structures. Bi NMs can be used in computed tomography (CT) imaging, photoacoustic (PA) imaging, and also in the fields of radiotherapy and phototherapy. Bi NMs can be designed in terms of composition, structure and surface modification to achieve the goal of having more patterns in cancer diagnosis and treatment. Despite their great success in the last decades, emerging nanomedicines still lack a complete comprehension regarding their safety issues and the connection among facets of physicochemical properties and safety. This review starts with the mechanism of action of Bi NMs, focusing on the main classes of Bi NMs biological effects and their toxicological mechanisms. And based on this information, principles for the development of safe-by-design nanomaterials for medical applications and recent advances in the field are outlined. These principles can be used as an initial step to direct the formulation of more effective and safer strategies based on Bi nanodrugs.
{"title":"Safe-by-design strategies towards bismuth-based nanomaterials in tumor diagnosis and therapy","authors":"Xiaoyu Zhang , Fene Gao , Yizhi Dai , Mingge Wang , Jing Liu","doi":"10.1016/j.nantod.2025.102714","DOIUrl":"10.1016/j.nantod.2025.102714","url":null,"abstract":"<div><div>The therapeutic nanomaterials (NMs) are receiving increasing attention for simultaneous diagnostic and therapeutic applications. Bismuth (Bi)-based NMs (Bi NMs) show excellent potential for building therapeutic platforms due to their sensitivity to X-ray, semiconducting properties, and unique structures. Bi NMs can be used in computed tomography (CT) imaging, photoacoustic (PA) imaging, and also in the fields of radiotherapy and phototherapy. Bi NMs can be designed in terms of composition, structure and surface modification to achieve the goal of having more patterns in cancer diagnosis and treatment. Despite their great success in the last decades, emerging nanomedicines still lack a complete comprehension regarding their safety issues and the connection among facets of physicochemical properties and safety. This review starts with the mechanism of action of Bi NMs, focusing on the main classes of Bi NMs biological effects and their toxicological mechanisms. And based on this information, principles for the development of safe-by-design nanomaterials for medical applications and recent advances in the field are outlined. These principles can be used as an initial step to direct the formulation of more effective and safer strategies based on Bi nanodrugs.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102714"},"PeriodicalIF":13.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-13DOI: 10.1016/j.nantod.2025.102710
Yating Qin , Yan Lin , Chao Tian , Yujie Qi , Shuling Wang , Xiaoyuan Chen , Wenxing Gu
Immune checkpoint blockade (ICB) therapy has emerged as a promising avenue for the treatment of malignant tumors. Nonetheless, the efficacy of this approach is constrained by low anti-tumor immunity and restricted intratumoral delivery of immune checkpoint inhibitors (ICIs) in solid tumors. In this study, a pH-responsive nanocomplex (BRM/PTX/aPD-1) was developed for the active transport of aPD-1 and PTX, thereby enhancing cancer chemoimmunotherapy. BRM/PTX/aPD-1 was prepared by using dynamic and reversible benzoic-imine bonds cross-linked bovine albumin (BSA), anti-PD-1 antibody (aPD-1) and PTX-loaded polylysine dendrimers. In the acidic tumor microenvironment, BRM/PTX/aPD-1 exhibited a charge reversal from negative to positive due to the hydrolysis of the β-carboxylic amide structure, which triggered cation-induced transcytosis. This process enabled active transport of adequate amounts of BRM/PTX/aPD-1 to the tumor parenchyma, where it was degraded by further hydrolysis of benzoic-imine bonds and effectively released aPD-1 and PTX. The nanocomplex demonstrated notable intratumoral permeability both in vitro and in vivo, particularly enhancing the delivery of aPD-1. Additionally, the nanocomplex showed robust anti-tumor activity in an orthotopic breast cancer model, significantly inhibiting tumor proliferation and preventing the progression of lung metastasis. This pH-responsive nanocomplex presents a promising platform for improved intratumoral delivery of ICIs and emerges as a practical solution for overcoming tumor immunosuppression.
{"title":"pH-responsive nanocomplex for active transport of aPD-1 and PTX to enhance cancer chemoimmunotherapy","authors":"Yating Qin , Yan Lin , Chao Tian , Yujie Qi , Shuling Wang , Xiaoyuan Chen , Wenxing Gu","doi":"10.1016/j.nantod.2025.102710","DOIUrl":"10.1016/j.nantod.2025.102710","url":null,"abstract":"<div><div>Immune checkpoint blockade (ICB) therapy has emerged as a promising avenue for the treatment of malignant tumors. Nonetheless, the efficacy of this approach is constrained by low anti-tumor immunity and restricted intratumoral delivery of immune checkpoint inhibitors (ICIs) in solid tumors. In this study, a pH-responsive nanocomplex (BRM/PTX/aPD-1) was developed for the active transport of aPD-1 and PTX, thereby enhancing cancer chemoimmunotherapy. BRM/PTX/aPD-1 was prepared by using dynamic and reversible benzoic-imine bonds cross-linked bovine albumin (BSA), anti-PD-1 antibody (aPD-1) and PTX-loaded polylysine dendrimers. In the acidic tumor microenvironment, BRM/PTX/aPD-1 exhibited a charge reversal from negative to positive due to the hydrolysis of the β-carboxylic amide structure, which triggered cation-induced transcytosis. This process enabled active transport of adequate amounts of BRM/PTX/aPD-1 to the tumor parenchyma, where it was degraded by further hydrolysis of benzoic-imine bonds and effectively released aPD-1 and PTX. The nanocomplex demonstrated notable intratumoral permeability both <em>in vitro</em> and <em>in vivo</em>, particularly enhancing the delivery of aPD-1. Additionally, the nanocomplex showed robust anti-tumor activity in an orthotopic breast cancer model, significantly inhibiting tumor proliferation and preventing the progression of lung metastasis. This pH-responsive nanocomplex presents a promising platform for improved intratumoral delivery of ICIs and emerges as a practical solution for overcoming tumor immunosuppression.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102710"},"PeriodicalIF":13.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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