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Augmenting Tumor Lysis and Immune Response through HIFU-armed Oncolytic Virus Delivery System
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-12-02 DOI: 10.1016/j.nantod.2024.102571
Xifeng Qin , Mingyang Liu , Hu Wu , Boshu Ouyang , Xu Zhao , Xiaomin Su , Ruizhe Xu , Huiwen Liu , Jiayi Wu , Yue Liu , Ting Wang , Onder Ergonul , Füsun Can , Jia Li , Lin Lin , Funan Liu , Zhiqing Pang
Oncolytic viruses (OVs) have hold great promise as a tumor immunotherapy. However, their effectiveness is hindered by the challenge of precise and efficient delivery in vivo and stimulating a robust anti-tumor immune response. In this study, we developed a strategy of high-intensity focused ultrasound (HIFU)-armed oncolytic immunotherapy. It was found that HIFU facilitating efficient delivery of erythrocyte-hijacking OVs to solid tumors and enhancing the penetration of OVs in tumors. Remarkably, HIFU enhanced the oncolytic effect of OVs not only by suppressing the host cell’s ability of virus clearance through downregulating the IFN signaling pathway, but also by enhancing OV replication within tumor cells through upregulating the expression of the oncogene RAS, inducing DNA damage, and promoting OVs-induced autophagy. More importantly, HIFU augmented OVs-mediated anti-tumor immune responses in vivo, leading to remodeling of the tumor microenvironment, resulting in nearly complete tumor regression (97.6 %) within 15 days and 80 % tumor-free status sustained for 120 days. Overall, these findings highlight the potential of HIFU as a novel modality for precise OV delivery, augmented oncolytic effect, and robust immunostimulation in oncolytic immunotherapy of solid tumors.
{"title":"Augmenting Tumor Lysis and Immune Response through HIFU-armed Oncolytic Virus Delivery System","authors":"Xifeng Qin ,&nbsp;Mingyang Liu ,&nbsp;Hu Wu ,&nbsp;Boshu Ouyang ,&nbsp;Xu Zhao ,&nbsp;Xiaomin Su ,&nbsp;Ruizhe Xu ,&nbsp;Huiwen Liu ,&nbsp;Jiayi Wu ,&nbsp;Yue Liu ,&nbsp;Ting Wang ,&nbsp;Onder Ergonul ,&nbsp;Füsun Can ,&nbsp;Jia Li ,&nbsp;Lin Lin ,&nbsp;Funan Liu ,&nbsp;Zhiqing Pang","doi":"10.1016/j.nantod.2024.102571","DOIUrl":"10.1016/j.nantod.2024.102571","url":null,"abstract":"<div><div>Oncolytic viruses (OVs) have hold great promise as a tumor immunotherapy. However, their effectiveness is hindered by the challenge of precise and efficient delivery <em>in vivo</em> and stimulating a robust anti-tumor immune response. In this study, we developed a strategy of high-intensity focused ultrasound (HIFU)-armed oncolytic immunotherapy. It was found that HIFU facilitating efficient delivery of erythrocyte-hijacking OVs to solid tumors and enhancing the penetration of OVs in tumors. Remarkably, HIFU enhanced the oncolytic effect of OVs not only by suppressing the host cell’s ability of virus clearance through downregulating the IFN signaling pathway, but also by enhancing OV replication within tumor cells through upregulating the expression of the oncogene RAS, inducing DNA damage, and promoting OVs-induced autophagy. More importantly, HIFU augmented OVs-mediated anti-tumor immune responses <em>in vivo</em>, leading to remodeling of the tumor microenvironment, resulting in nearly complete tumor regression (97.6 %) within 15 days and 80 % tumor-free status sustained for 120 days. Overall, these findings highlight the potential of HIFU as a novel modality for precise OV delivery, augmented oncolytic effect, and robust immunostimulation in oncolytic immunotherapy of solid tumors.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"61 ","pages":"Article 102571"},"PeriodicalIF":13.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759427","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}
引用次数: 0
Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-12-01 DOI: 10.1016/S1748-0132(24)00426-2
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引用次数: 0
Inside Back Cover - Graphical abstract TOC/TOC in double column continued from OBC if required, otherwise blank page
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-12-01 DOI: 10.1016/S1748-0132(24)00425-0
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引用次数: 0
Corrigendum to “Engineering catalytic dephosphorylation reaction for endotoxin inactivation” [Nano Today 44 (2022) 101456]
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-12-01 DOI: 10.1016/j.nantod.2024.102525
Meng Gao , Xi Liu , Zhenzhen Wang , Hui Wang , Tristan Asset , Di Wu , Jun Jiang , Qianqian Xie , Shujuan Xu , Xiaoming Cai , Jia Li , Weili Wang , Huizhen Zheng , Xingfa Gao , Nikolai Tarasenko , Benjamin Rotonnelli , Jean-Jacques Gallet , Frédéric Jaouen , Ruibin Li
{"title":"Corrigendum to “Engineering catalytic dephosphorylation reaction for endotoxin inactivation” [Nano Today 44 (2022) 101456]","authors":"Meng Gao ,&nbsp;Xi Liu ,&nbsp;Zhenzhen Wang ,&nbsp;Hui Wang ,&nbsp;Tristan Asset ,&nbsp;Di Wu ,&nbsp;Jun Jiang ,&nbsp;Qianqian Xie ,&nbsp;Shujuan Xu ,&nbsp;Xiaoming Cai ,&nbsp;Jia Li ,&nbsp;Weili Wang ,&nbsp;Huizhen Zheng ,&nbsp;Xingfa Gao ,&nbsp;Nikolai Tarasenko ,&nbsp;Benjamin Rotonnelli ,&nbsp;Jean-Jacques Gallet ,&nbsp;Frédéric Jaouen ,&nbsp;Ruibin Li","doi":"10.1016/j.nantod.2024.102525","DOIUrl":"10.1016/j.nantod.2024.102525","url":null,"abstract":"","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102525"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743148","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}
引用次数: 0
Sequentially amplified integration of catalytic DNA circuits for high-performance intracellular imaging of miRNA and interpretation of mRNA-miRNA signalling pathway
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-12-01 DOI: 10.1016/j.nantod.2024.102563
Mengdi Yu , Yushi Wang , Jinhua Shang , Qingqing Zhang , Yuqian Jiang , Xiaoqing Liu , Fuan Wang
The cascaded catalytic circuits are viable tools for improving the signal gain of biosensors, yet their sensing performance is still limited by the signal leakage from complex biological environment and unsatisfying reaction efficiency from inter-reactants steric hindrance. Herein, we proposed a catalytically localized DNA (CLD) circuit for the accurate and high-efficiency imaging of microRNA (miRNA) in living cells by virtue of the sequentially and successively amplified integration of catalytic DNA circuits. The compact CLD circuit was constructed by integrating two elemental catalytic circuits, cell-responsive EDR module and analyte-sensing CHA module, where CHA module was initially caged in EDR module for eliminating the unwanted off-site and off-target signal leakage. Only by cell-specific messenger RNA (mRNA)-activated EDR operation then the elemental CHA circuit could be successively connected to facilitate the highly efficient intramolecular reaction with low steric hindrance, thus leading to accelerated reaction efficiency for miRNA analyte. The multiple molecular recognition and the spatial self-confinement of the smart CLD circuit enable the accurate and high-efficiency imaging of intracellular miRNA. The interaction network of mRNA and miRNA was then investigated in situ through our CLD circuit, which provides a powerful tool for discovering the underlying signal pathways between these different RNAs in living cells.
{"title":"Sequentially amplified integration of catalytic DNA circuits for high-performance intracellular imaging of miRNA and interpretation of mRNA-miRNA signalling pathway","authors":"Mengdi Yu ,&nbsp;Yushi Wang ,&nbsp;Jinhua Shang ,&nbsp;Qingqing Zhang ,&nbsp;Yuqian Jiang ,&nbsp;Xiaoqing Liu ,&nbsp;Fuan Wang","doi":"10.1016/j.nantod.2024.102563","DOIUrl":"10.1016/j.nantod.2024.102563","url":null,"abstract":"<div><div>The cascaded catalytic circuits are viable tools for improving the signal gain of biosensors, yet their sensing performance is still limited by the signal leakage from complex biological environment and unsatisfying reaction efficiency from inter-reactants steric hindrance. Herein, we proposed a catalytically localized DNA (CLD) circuit for the accurate and high-efficiency imaging of microRNA (miRNA) in living cells by virtue of the sequentially and successively amplified integration of catalytic DNA circuits. The compact CLD circuit was constructed by integrating two elemental catalytic circuits, cell-responsive EDR module and analyte-sensing CHA module, where CHA module was initially caged in EDR module for eliminating the unwanted off-site and off-target signal leakage. Only by cell-specific messenger RNA (mRNA)-activated EDR operation then the elemental CHA circuit could be successively connected to facilitate the highly efficient intramolecular reaction with low steric hindrance, thus leading to accelerated reaction efficiency for miRNA analyte. The multiple molecular recognition and the spatial self-confinement of the smart CLD circuit enable the accurate and high-efficiency imaging of intracellular miRNA. The interaction network of mRNA and miRNA was then investigated in situ through our CLD circuit, which provides a powerful tool for discovering the underlying signal pathways between these different RNAs in living cells.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"61 ","pages":"Article 102563"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757085","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}
引用次数: 0
RVG29-modified oncolytic herpes simplex virus for intracranial tumor treatment
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-11-30 DOI: 10.1016/j.nantod.2024.102573
Liting Chen , Chen Xu , Hainan Xu , Hongyu Liu , Zihan Ma , Jiahao Liu , Xiaoyu Gao , Wei Lv , Xinze Du , Xiao Zhao , Jing Shi , Keman Cheng , Funan Liu
Oncolytic virus therapy for brain tumors has achieved breakthrough progress in clinical applications, yet its potential is severely constrained by the mode of administration-direct intratumoral injection into the cranial cavity. Other administration routes face rapid clearance by neutralizing antibodies and obstacles posed by the blood-brain barrier. Herein, we engineered the oncolytic herpes simplex virus type 2 (OH2) with surface modifications of polyethylene glycol (PEG) and rabies virus glycoprotein 29 (RVG29, a BBB-penetrating peptide from the rabies virus), to form OH2-PEG-RVG. OH2-PEG-RVG could efficiently traversed the blood-brain barrier even in BALB/c mice with pre-existing anti-OH2 antibodies, leading to the accumulation of OH2 in the brain. More importantly, OH2-PEG-RVG maintained blood-brain barrier integrity without causing pathological changes or behavioral abnormalities in mice. Furthermore, OH2-PEG-RVG effectively inhibited brain tumor growth, transforming immunologically "cold" tumors into "hot" tumors, inducing a robust anti-tumor immune response, and prolonging the survival of the mice. These findings underscore the potential of OH2-PEG-RVG as a multifaceted therapeutic strategy for effective brain tumor treatment, offering insights into addressing blood-brain barrier limitations.
{"title":"RVG29-modified oncolytic herpes simplex virus for intracranial tumor treatment","authors":"Liting Chen ,&nbsp;Chen Xu ,&nbsp;Hainan Xu ,&nbsp;Hongyu Liu ,&nbsp;Zihan Ma ,&nbsp;Jiahao Liu ,&nbsp;Xiaoyu Gao ,&nbsp;Wei Lv ,&nbsp;Xinze Du ,&nbsp;Xiao Zhao ,&nbsp;Jing Shi ,&nbsp;Keman Cheng ,&nbsp;Funan Liu","doi":"10.1016/j.nantod.2024.102573","DOIUrl":"10.1016/j.nantod.2024.102573","url":null,"abstract":"<div><div>Oncolytic virus therapy for brain tumors has achieved breakthrough progress in clinical applications, yet its potential is severely constrained by the mode of administration-direct intratumoral injection into the cranial cavity. Other administration routes face rapid clearance by neutralizing antibodies and obstacles posed by the blood-brain barrier. Herein, we engineered the oncolytic herpes simplex virus type 2 (OH2) with surface modifications of polyethylene glycol (PEG) and rabies virus glycoprotein 29 (RVG29, a BBB-penetrating peptide from the rabies virus), to form OH2-PEG-RVG. OH2-PEG-RVG could efficiently traversed the blood-brain barrier even in BALB/c mice with pre-existing anti-OH2 antibodies, leading to the accumulation of OH2 in the brain. More importantly, OH2-PEG-RVG maintained blood-brain barrier integrity without causing pathological changes or behavioral abnormalities in mice. Furthermore, OH2-PEG-RVG effectively inhibited brain tumor growth, transforming immunologically \"cold\" tumors into \"hot\" tumors, inducing a robust anti-tumor immune response, and prolonging the survival of the mice. These findings underscore the potential of OH2-PEG-RVG as a multifaceted therapeutic strategy for effective brain tumor treatment, offering insights into addressing blood-brain barrier limitations.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"61 ","pages":"Article 102573"},"PeriodicalIF":13.2,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746662","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}
引用次数: 0
Boosting ubiquitin-proteasome system-mediated androgen receptor degradation and cGAS-STING pathway activation for synergistic prostate cancer therapy by engineered zinc-manganese oxide nanoparticles
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-11-29 DOI: 10.1016/j.nantod.2024.102560
Linnan Yang , Yi Hu , Hui Peng , Zhengbin Wang , Sixu Chen , Jieying Qian , Yujie Yang , Zhonghua Xu , Jin Wu , Chaozhao Liang , Guilong Zhang , Yunjiao Zhang , Li Zhang
Androgen receptor (AR) is an essential target for prostate cancer (PCa) therapy, while required resistance due to AR overexpression/abnormal splicing often leads to therapeutic failure, and how to realize the synergistic therapeutic efficacy for PCa remains a challenge. Herein, a novel paradigm of zinc-manganese oxide nanoparticles (ZMONPs) is rationally engineered, which can cooperate in promoting ubiquitin-proteasome system (UPS)-mediated AR degradation and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway activation, thereby generating a tumoricidal immune microenvironment to elicit PCa cell death. Upon lysosomal acidolysis, ZMONPs promote zinc ions overload to produce more reactive oxygen species (ROS), which ultimately contribute to UPS-mediated AR degradation and tumoricidal effect. In PCa mouse models, ZMONPs significantly down-regulate the abundance of AR within the tumor microenvironment, further facilitating cGAS-STING signaling pathway activation to secrete C-C motif chemokine ligand 5 (CCL5) and interferon beta (IFN-β), which enhance dendritic cells (DCs) maturation and cytotoxic T lymphocytes (CTLs) infiltration, thus realizing tumor growth inhibition in a cooperative manner. In addition, co-administration of ZMONPs and docetaxel presents notably synergistic therapeutic efficacy. Collectively, this study highlights the favorable effects of ZMONPs on AR degradation-related hormonal therapy and anti-tumor immunity, which may serve as a promising therapeutic strategy for PCa.
{"title":"Boosting ubiquitin-proteasome system-mediated androgen receptor degradation and cGAS-STING pathway activation for synergistic prostate cancer therapy by engineered zinc-manganese oxide nanoparticles","authors":"Linnan Yang ,&nbsp;Yi Hu ,&nbsp;Hui Peng ,&nbsp;Zhengbin Wang ,&nbsp;Sixu Chen ,&nbsp;Jieying Qian ,&nbsp;Yujie Yang ,&nbsp;Zhonghua Xu ,&nbsp;Jin Wu ,&nbsp;Chaozhao Liang ,&nbsp;Guilong Zhang ,&nbsp;Yunjiao Zhang ,&nbsp;Li Zhang","doi":"10.1016/j.nantod.2024.102560","DOIUrl":"10.1016/j.nantod.2024.102560","url":null,"abstract":"<div><div>Androgen receptor (AR) is an essential target for prostate cancer (PCa) therapy, while required resistance due to AR overexpression/abnormal splicing often leads to therapeutic failure, and how to realize the synergistic therapeutic efficacy for PCa remains a challenge. Herein, a novel paradigm of zinc-manganese oxide nanoparticles (ZMONPs) is rationally engineered, which can cooperate in promoting ubiquitin-proteasome system (UPS)-mediated AR degradation and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway activation, thereby generating a tumoricidal immune microenvironment to elicit PCa cell death. Upon lysosomal acidolysis, ZMONPs promote zinc ions overload to produce more reactive oxygen species (ROS), which ultimately contribute to UPS-mediated AR degradation and tumoricidal effect. In PCa mouse models, ZMONPs significantly down-regulate the abundance of AR within the tumor microenvironment, further facilitating cGAS-STING signaling pathway activation to secrete C-C motif chemokine ligand 5 (CCL5) and interferon beta (IFN-β), which enhance dendritic cells (DCs) maturation and cytotoxic T lymphocytes (CTLs) infiltration, thus realizing tumor growth inhibition in a cooperative manner. In addition, co-administration of ZMONPs and docetaxel presents notably synergistic therapeutic efficacy. Collectively, this study highlights the favorable effects of ZMONPs on AR degradation-related hormonal therapy and anti-tumor immunity, which may serve as a promising therapeutic strategy for PCa.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"61 ","pages":"Article 102560"},"PeriodicalIF":13.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747470","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}
引用次数: 0
SNA·SMNP·CBE system: A novel integrative strategy for β-hemoglobinopathies gene therapy SNA-SMNP-CBE 系统:β-血红蛋白病基因治疗的新型综合策略
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-11-26 DOI: 10.1016/j.nantod.2024.102558
Hongya Cheng , Wenqiao Hui , Hanyue Kang , Zhenni Shi , Jianlei Liu , Xin Wang , Fei Qi , Lin Mao , Huiqian Ding , Rongjian Hu , Nabila Begum , Daoqiang Lu , Dandan Chen , Xinyue Cheng , Miaomiao Wan , Dahai Liu , Hsian-Rong Tseng , Shoudong Ye , Xiaobin Xu , Baowei Zhang , Qian Ban
Here, we developed and demonstrated a novel integrative system—Silica Nanorods (SNA) substrate cell capture combined with Supramolecular Nanoparticle (SMNP) delivery mediated CBE base editing (SNA·SMNP·CBE)—achieving the synchronization of CD34+HSPCs cell capture and gene editing for β-hemoglobinopathies. First, in vitro study shows it enables efficient and precise modification of BCL11A promoter in CD34+HSPCs, yielding the highly editing efficiency of 50.4 %, thus making an alternative strategy to conventional immunomagnetic cell separation and electroporation transfection system mediated CBE editing (IMS·EP·CBE). Then, we transplanted the edited human CD34+HSPCs into severe combined immunodeficiency (SCID) mice by using intraosseous injection strategy. When compared with conventional IMS·EP·CBE methods, our results showed that significantly higher human HBG expression in the bone marrow and peripheral blood of recipient mice, and long-term engraftment, evidenced from similar gene expression profiles to naïve CD34+HSPCs at 14 weeks. Conclusively, our integrative system—SNA·SMNP·CBE·intraosseous injection—offers an appealing novel way for the unique potential of gene therapy in the clinic application for β-hemoglobinopathies patients.
在这里,我们开发并展示了一种新型的整合系统--二氧化硅纳米棒(SNA)基底细胞捕获结合超分子纳米颗粒(SMNP)递送介导的CBE碱基编辑(SNA-SMNP-CBE)--实现了CD34+HSPCs细胞捕获与β-血红蛋白病基因编辑的同步。首先,体外研究表明它能高效、精确地修饰 CD34+HSPCs 的 BCL11A 启动子,编辑效率高达 50.4%,从而成为传统免疫磁性细胞分离和电穿孔转染系统介导的 CBE 编辑(IMS-EP-CBE)的替代策略。然后,我们采用骨内注射策略将编辑后的人 CD34+HSPCs 移植到重症联合免疫缺陷(SCID)小鼠体内。与传统的 IMS-EP-CBE 方法相比,我们的研究结果表明,受体小鼠骨髓和外周血中的人 HBG 表达量显著提高,并且在 14 周时,受体小鼠的基因表达谱与天真 CD34+HSPCs 相似,这证明了我们的研究结果具有长期的移植效果。总之,我们的综合系统--SNA-SMNP-CBE-骨内注射--为β-血红蛋白病患者的临床应用提供了一种具有独特潜力的基因治疗新方法。
{"title":"SNA·SMNP·CBE system: A novel integrative strategy for β-hemoglobinopathies gene therapy","authors":"Hongya Cheng ,&nbsp;Wenqiao Hui ,&nbsp;Hanyue Kang ,&nbsp;Zhenni Shi ,&nbsp;Jianlei Liu ,&nbsp;Xin Wang ,&nbsp;Fei Qi ,&nbsp;Lin Mao ,&nbsp;Huiqian Ding ,&nbsp;Rongjian Hu ,&nbsp;Nabila Begum ,&nbsp;Daoqiang Lu ,&nbsp;Dandan Chen ,&nbsp;Xinyue Cheng ,&nbsp;Miaomiao Wan ,&nbsp;Dahai Liu ,&nbsp;Hsian-Rong Tseng ,&nbsp;Shoudong Ye ,&nbsp;Xiaobin Xu ,&nbsp;Baowei Zhang ,&nbsp;Qian Ban","doi":"10.1016/j.nantod.2024.102558","DOIUrl":"10.1016/j.nantod.2024.102558","url":null,"abstract":"<div><div>Here, we developed and demonstrated a novel integrative system—Silica Nanorods (SNA) substrate cell capture combined with Supramolecular Nanoparticle (SMNP) delivery mediated CBE base editing (SNA·SMNP·CBE)—achieving the synchronization of CD34+HSPCs cell capture and gene editing for β-hemoglobinopathies. First, <em>in vitro</em> study shows it enables efficient and precise modification of BCL11A promoter in CD34+HSPCs, yielding the highly editing efficiency of 50.4 %, thus making an alternative strategy to conventional immunomagnetic cell separation and electroporation transfection system mediated CBE editing (IMS·EP·CBE). Then, we transplanted the edited human CD34+HSPCs into severe combined immunodeficiency (SCID) mice by using intraosseous injection strategy. When compared with conventional IMS·EP·CBE methods, our results showed that significantly higher human HBG expression in the bone marrow and peripheral blood of recipient mice, and long-term engraftment, evidenced from similar gene expression profiles to naïve CD34+HSPCs at 14 weeks. Conclusively, our integrative system—SNA·SMNP·CBE·intraosseous injection—offers an appealing novel way for the unique potential of gene therapy in the clinic application for β-hemoglobinopathies patients.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"61 ","pages":"Article 102558"},"PeriodicalIF":13.2,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721116","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}
引用次数: 0
Arrays of horizontal semiconducting carbon nanotubes grown from non-metal catalysts prepared by a “thermophoresis-anchoring” synergistic strategy 利用 "热泳-锚定 "协同策略制备的非金属催化剂生长的水平半导体碳纳米管阵列
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-11-26 DOI: 10.1016/j.nantod.2024.102562
Sizhe Lin , Tao Ye , Xinyu Zhang , Hui Zuo , Linxi Zhu , Xiuxia Wang , Changlong Li , Zhi Yang , Ran Du , Dewu Lin , Yue Hu
The fabrication of uncontaminated single-walled carbon nanotube (SWNT) horizontal arrays is crucial for the development of carbon-based nanoelectronics. However, chemical vapor deposition (CVD) using transition metal catalysts, one of the main methods for preparing SWNT arrays, leaves a significant amount of metal impurities. Here, we report a synergistic thermophoresis-anchoring strategy to prepare uniformly dispersed and size-controllable non-metal SiOx catalysts for the growth of horizontal SWNT arrays. The pyrolysis of silicon-based precursors generates an abundant supply of SiOx particles, which are deposited bottom-up onto the quartz substrate due to the thermal buoyancy induced by a rapid temperature increase. Meanwhile, Surface reconstruction promoted by mechanical force creates numerous anchoring sites on the quartz substrate. This facilitates the capture of catalysts and suppresses their migration and aggregation, thereby promoting the uniform deposition of small-sized catalysts. Consequently, SWNT arrays with a density of 9 tubes per micron are synthesized using these nonmetal SiOx catalysts. Importantly, Raman spectroscopy and electrical characterization reveal a semiconductor ratio of up to 94 % for the directly grown SWNT arrays, which is attributed to an in situ etching mechanism within the confined space. This work provides a viable way to promote the practical application of next-generation carbon-based nanodevices.
制备无污染的单壁碳纳米管(SWNT)水平阵列对于开发碳基纳米电子学至关重要。然而,使用过渡金属催化剂进行化学气相沉积(CVD)是制备 SWNT 阵列的主要方法之一,但会留下大量金属杂质。在此,我们报告了一种热泳-锚定协同策略,用于制备均匀分散、尺寸可控的非金属氧化硅催化剂,以生长水平的 SWNT 阵列。硅基前驱体的热解产生了大量的氧化硅颗粒,这些颗粒在温度快速升高所产生的热浮力作用下自下而上地沉积到石英基底上。同时,机械力促进的表面重构在石英基底上形成了许多锚定点。这有利于捕获催化剂,抑制其迁移和聚集,从而促进小尺寸催化剂的均匀沉积。因此,使用这些非金属氧化硅催化剂合成的 SWNT 阵列密度为每微米 9 根。重要的是,拉曼光谱和电学特性分析表明,直接生长的 SWNT 阵列的半导体比率高达 94%,这归因于密闭空间内的原位蚀刻机制。这项工作为促进下一代碳基纳米器件的实际应用提供了一条可行的途径。
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引用次数: 0
Blue phosphorescent solid supramolecular assemblies between hydroxypropyl-β-cyclodextrin and triazine derivatives for achieving multicolor delayed fluorescence 用于实现多色延迟荧光的羟丙基-β-环糊精和三嗪衍生物之间的蓝色磷光固体超分子组装体
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-11-24 DOI: 10.1016/j.nantod.2024.102561
Xuan Zhao, Xiaolu Zhou, Qingwen Cheng, Yu Liu
Highly efficient blue phosphorescent solid supramolecular assemblies are constructed by three triazine derivatives with different carboxylate substitution positions (TAB, TAC and TAD), hydroxypropyl-β-cyclodextrin (HPCD) and polyvinyl alcohol (PVA). The encapsulation of HPCD to TAB/C/D effectively promotes phosphorescence lifetimes and quantum yields of the guests by the host-guest interaction and hydrogen bonds suppressing the nonradiative decays. Impressively, TAD-HPCD/PVA with blue phosphorescence boasts an ultrahigh phosphorescence quantum yield (ΦP) of 71.65 %. By further separately doping with fluorescent dyes Fluorescein sodium, Rhodamine B and Sulfo-Cyanine5, supramolecular polymeric films with water responsiveness, regulable lifetimes and multicolor delayed fluorescence are obtained via triplet-to-singlet and singlet-to-singlet Förster resonance energy transfer. Polymeric phosphorescence supramolecular materials mediated by HPCD are desirable for optical anti-counterfeiting patterns and information encryption.
三种具有不同羧基取代位置的三嗪衍生物(TAB、TAC 和 TAD)、羟丙基-β-环糊精(HPCD)和聚乙烯醇(PVA)构建了高效的蓝色磷光固体超分子组装体。HPCD 与 TAB/C/D 的封装通过主客体相互作用和氢键抑制非辐射衰减,有效地提高了客体的磷光寿命和量子产率。令人印象深刻的是,具有蓝色磷光的 TAD-HPCD/PVA 拥有 71.65 % 的超高磷光量子产率(ΦP)。通过进一步分别掺杂荧光染料荧光素钠、罗丹明 B 和磺基青绿素 5,并通过三重子对小卫星和单重子对小卫星的佛斯特共振能量转移,得到了具有水响应性、可调寿命和多色延迟荧光的超分子聚合物薄膜。由 HPCD 介导的聚合物磷光超分子材料有望用于光学防伪图案和信息加密。
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引用次数: 0
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