Pub Date : 2024-10-05DOI: 10.1016/j.nantod.2024.102520
Jie Gao , Shangli Ding , Ling Chen , Hongyu Li , Wen-Chao Geng , Dong-Sheng Guo , Zeli Yuan
High-performance organic photothermal agents (PTAs) hinges primarily on manipulating non-radiative decay processes, which typically necessitates intricate and time-intensive molecular engineering. The main challenge is how to bring dye and quencher into close molecular contact at a sub-nanometer distance for effective quenching. A host-guest strategy is presented to fabricate supramolecular PTAs by non-radiative electron transfer. Through strong complexation of dye with a “black hole host”, quaternary-ammonium modified calix[4]arene tetraoctyloxy ether (QC4A-8C), photothermal performances of ten distinct dyes were optimized to an unprecedented degree. The potential of supramolecular PTAs in biological application was evaluated photothermal therapy in vitro and in vivo using zinc tetrasulfonate phthalocyanine@QC4A-8C. This study provides insights into leveraging existing dyes to augment photothermal effects through electron transfer, offering a streamlined pathway for the development of safe and efficient supramolecular PTAs.
{"title":"Supramolecular photothermal agents mediated by black hole hosts","authors":"Jie Gao , Shangli Ding , Ling Chen , Hongyu Li , Wen-Chao Geng , Dong-Sheng Guo , Zeli Yuan","doi":"10.1016/j.nantod.2024.102520","DOIUrl":"10.1016/j.nantod.2024.102520","url":null,"abstract":"<div><div>High-performance organic photothermal agents (PTAs) hinges primarily on manipulating non-radiative decay processes, which typically necessitates intricate and time-intensive molecular engineering. The main challenge is how to bring dye and quencher into close molecular contact at a sub-nanometer distance for effective quenching. A host-guest strategy is presented to fabricate supramolecular PTAs by non-radiative electron transfer. Through strong complexation of dye with a “black hole host”, quaternary-ammonium modified calix[4]arene tetraoctyloxy ether (QC4A-8C), photothermal performances of ten distinct dyes were optimized to an unprecedented degree. The potential of supramolecular PTAs in biological application was evaluated photothermal therapy in vitro and in vivo using zinc tetrasulfonate phthalocyanine@QC4A-8C. This study provides insights into leveraging existing dyes to augment photothermal effects through electron transfer, offering a streamlined pathway for the development of safe and efficient supramolecular PTAs.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102520"},"PeriodicalIF":13.2,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142422015","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 : 2024-10-03DOI: 10.1016/j.nantod.2024.102516
Haolai Mao , Xue Jin , Chengxi Li , Chengyu Jiang , Xuefeng Yang , Zhijie Wang , Da-Wei Fu , Yi Zhang , Pengfei Duan
Optically active persistent luminescent materials have attracted significant attention due to their distinctive luminescent characteristics and ability to exhibit rich circular polarization information. Despite extensive efforts to develop circularly polarized persistent luminescence (CPPL) materials using chiral molecules or polymers, fabricating CPPL materials from achiral units remains a big challenge. In this work, we introduce an efficient co-assembly strategy to create CPPL materials using entirely achiral organic molecules. The optical activities of co-assembled complexes are attributed to structural chirality, which arises from chiral nanohelices formed during symmetry breaking in the self-assembly process of C3-symmetric molecules. Achiral molecules with long-lasting phosphorescence can adhere to these chiral nanostructures via hydrogen bonding, and during the drying phase, form nanocrystals that align along helical fibers, resulting in circularly polarized, long-lasting phosphorescence. Enhanced CPPL efficiency, ranging from blue to yellow with a dissymmetry factor over 1.2 × 10−2 and lifetime of up to 0.6 s at room temperature, is achieved through hydrogen bonding driven co-assembly. Additionally, the CPPL spectra of these co-assemblies are captured using a homemade time-resolved circularly polarized long afterglow detection platform. This study not only presents a new approach for the high-efficiency design of CPPL materials from achiral building blocks but also significantly broadens the research possibilities in real-time CPPL analysis, offering a horizon in the exploration of CPPL materials.
{"title":"Optically active persistent luminescence in supramolecular nanoassemblies constructed from entirely achiral building blocks","authors":"Haolai Mao , Xue Jin , Chengxi Li , Chengyu Jiang , Xuefeng Yang , Zhijie Wang , Da-Wei Fu , Yi Zhang , Pengfei Duan","doi":"10.1016/j.nantod.2024.102516","DOIUrl":"10.1016/j.nantod.2024.102516","url":null,"abstract":"<div><div>Optically active persistent luminescent materials have attracted significant attention due to their distinctive luminescent characteristics and ability to exhibit rich circular polarization information. Despite extensive efforts to develop circularly polarized persistent luminescence (CPPL) materials using chiral molecules or polymers, fabricating CPPL materials from achiral units remains a big challenge. In this work, we introduce an efficient co-assembly strategy to create CPPL materials using entirely achiral organic molecules. The optical activities of co-assembled complexes are attributed to structural chirality, which arises from chiral nanohelices formed during symmetry breaking in the self-assembly process of <em>C</em><sub>3</sub>-symmetric molecules. Achiral molecules with long-lasting phosphorescence can adhere to these chiral nanostructures via hydrogen bonding, and during the drying phase, form nanocrystals that align along helical fibers, resulting in circularly polarized, long-lasting phosphorescence. Enhanced CPPL efficiency, ranging from blue to yellow with a dissymmetry factor over 1.2 × 10<sup>−2</sup> and lifetime of up to 0.6 s at room temperature, is achieved through hydrogen bonding driven co-assembly. Additionally, the CPPL spectra of these co-assemblies are captured using a homemade time-resolved circularly polarized long afterglow detection platform. This study not only presents a new approach for the high-efficiency design of CPPL materials from achiral building blocks but also significantly broadens the research possibilities in real-time CPPL analysis, offering a horizon in the exploration of CPPL materials.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102516"},"PeriodicalIF":13.2,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421448","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 : 2024-10-03DOI: 10.1016/j.nantod.2024.102518
Yuan Li , Yishi Tian , Chanjuan Li , Wenli Fang , Xiaohong Li , Zhangyan Jing , Zhaoxin Yang , Xiaozhou Zhang , Yanlan Huang , Jiaqi Gong , Fanqiang Meng , Lin Qi , Xin Liang , Linlin Hou , Kai Lv , Xudong Zhang
Chimeric antigen receptor (CAR) T cell therapy has implemented impressive advances in the treatment of B-cell lymphoma. However, the complex production process of CAR T cells and hindrance of solid tumor penetration remain substantial challenges. Intriguingly, cell-targeting delivery of messenger RNA (mRNA) with ionizable lipid nanoparticles (mRNA-LNPs) is able to efficiently and precisely engineer T cells and other immune cells in vivo to perform their functions. Herein, we harnessed the ionizable LNPs to encapsulate mRNA encoding anti-tyrosinase related protein 1 (TRP1) CAR (CAR-LNPs) for in vivo generation of mRNA-CAR T cells to eliminate melanoma cells. Specifically, the anti-CD3 antibody (aCD3) armed mRNA-LNPs (CD3-mRNA-LNPs) selectively targeted T cells, resulting in the production of functional and therapeutic levels of CAR T cells both ex vivo and in vivo. These CD3-CAR-LNPs engineered CAR T cells were capable of infiltrating into the solid tumor and effectively eliminating melanoma cells with high TRP1 expression, significantly hindering tumor progression. Critically, CD3–7CAR-LNPs containing mRNA encoding both CAR and interleukin-7 (IL-7) generated 7CAR T cells that secreted IL-7, thereby enhancing the activity and proliferation of both CAR T cells and other intratumoral cytotoxic T cells. Alternatively, the employment of anti-programmed cell death protein 1 antibody (aPD-1) protected mRNA-CAR T cells from exhaustion, especially in combination with CD3–7CAR-LNPs, could significantly enhance the antitumor capability of CAR T cells without causing acute cytokine release syndrome (CRS).
嵌合抗原受体（CAR）T 细胞疗法在治疗 B 细胞淋巴瘤方面取得了令人瞩目的进展。然而，CAR T 细胞复杂的生产过程和对实体瘤穿透的阻碍仍然是巨大的挑战。有趣的是，利用可离子化脂质纳米颗粒（mRNA-LNPs）进行细胞靶向递送信使核糖核酸（mRNA）能够高效、精确地改造体内的T细胞和其他免疫细胞，使其发挥功能。在这里，我们利用可离子化的 LNPs 封装了编码抗酪氨酸酶相关蛋白 1（TRP1）CAR 的 mRNA（CAR-LNPs），用于在体内生成 mRNA-CAR T 细胞以消灭黑色素瘤细胞。具体来说，抗 CD3 抗体（aCD3）武装的 mRNA-LNPs （CD3-mRNA-LNPs）可选择性地靶向 T 细胞，从而在体内外产生功能性和治疗水平的 CAR T 细胞。这些 CD3-CAR-LNPs 工程化 CAR T 细胞能够渗入实体瘤，并有效清除 TRP1 高表达的黑色素瘤细胞，从而大大阻碍了肿瘤的进展。重要的是，CD3-7CAR-LNPs含有编码CAR和白细胞介素-7（IL-7）的mRNA，能产生分泌IL-7的7CAR T细胞，从而增强CAR T细胞和其他瘤内细胞毒性T细胞的活性和增殖。另外，使用抗程序性细胞死亡蛋白 1 抗体（aPD-1）可保护 mRNA-CAR T 细胞免于衰竭，尤其是与 CD3-7CAR-LNPs 结合使用时，可显著增强 CAR T 细胞的抗肿瘤能力，而不会引起急性细胞因子释放综合征（CRS）。
{"title":"In situ engineering of mRNA-CAR T cells using spleen-targeted ionizable lipid nanoparticles to eliminate cancer cells","authors":"Yuan Li , Yishi Tian , Chanjuan Li , Wenli Fang , Xiaohong Li , Zhangyan Jing , Zhaoxin Yang , Xiaozhou Zhang , Yanlan Huang , Jiaqi Gong , Fanqiang Meng , Lin Qi , Xin Liang , Linlin Hou , Kai Lv , Xudong Zhang","doi":"10.1016/j.nantod.2024.102518","DOIUrl":"10.1016/j.nantod.2024.102518","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) T cell therapy has implemented impressive advances in the treatment of B-cell lymphoma. However, the complex production process of CAR T cells and hindrance of solid tumor penetration remain substantial challenges. Intriguingly, cell-targeting delivery of messenger RNA (mRNA) with ionizable lipid nanoparticles (mRNA-LNPs) is able to efficiently and precisely engineer T cells and other immune cells <em>in vivo</em> to perform their functions. Herein, we harnessed the ionizable LNPs to encapsulate mRNA encoding anti-tyrosinase related protein 1 (TRP1) CAR (CAR-LNPs) for <em>in vivo</em> generation of mRNA-CAR T cells to eliminate melanoma cells. Specifically, the anti-CD3 antibody (aCD3) armed mRNA-LNPs (CD3-mRNA-LNPs) selectively targeted T cells, resulting in the production of functional and therapeutic levels of CAR T cells both <em>ex vivo</em> and <em>in vivo</em>. These CD3-CAR-LNPs engineered CAR T cells were capable of infiltrating into the solid tumor and effectively eliminating melanoma cells with high TRP1 expression, significantly hindering tumor progression. Critically, CD3–7CAR-LNPs containing mRNA encoding both CAR and interleukin-7 (IL-7) generated 7CAR T cells that secreted IL-7, thereby enhancing the activity and proliferation of both CAR T cells and other intratumoral cytotoxic T cells. Alternatively, the employment of anti-programmed cell death protein 1 antibody (aPD-1) protected mRNA-CAR T cells from exhaustion, especially in combination with CD3–7CAR-LNPs, could significantly enhance the antitumor capability of CAR T cells without causing acute cytokine release syndrome (CRS).</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102518"},"PeriodicalIF":13.2,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421449","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 : 2024-10-02DOI: 10.1016/j.nantod.2024.102511
Miao Zhang , Yuting Wen , Zhongxing Zhang , Xia Song , Jingling Zhu , Chitinart Thedrattanawong , Hongzhen Bai , Guping Tang , Kazushi Ogata , Shin-ichi Yusa , Jun Li
Amphiphilic block polymers have the ability to self-assemble and form nanomicelles, which have been extensively studied as nanocarriers for improving the bioavailability and biodistribution of chemotherapeutic drugs while reducing systemic toxicity. However, polymer micelles often face issues with poor stability in the bloodstream, leading to a short circulation time and leakage of the payload. Here, this work reports a rational design of a sharp-contrast Janus star polymer (SJSP) consisting of multiple arms of superhydrophobic lipid moieties and superhydrophilic polyzwitterion chains attached to a β-cyclodextrin core. The SJSP polymer forms nanomicelles possessing a stable core and a controllable and dense stealth shell that effectively protects them in the bloodstream, preventing payload leakage and blood protein adsorption. It is demonstrated that the hydrophobic/hydrophilic balance can be optimized to achieve strong micellar assembly by adjusting the number of lipid and polyzwitterion arms. The SJSP micelle system shows significantly longer blood circulation time in vivo compared to linear counterparts and other available amphiphilic block copolymer micelle systems. Therefore, the SJSP micelle design offers a promising strategy for developing nanocarriers with potential for translational applications in vivo.
{"title":"Long in vivo circulating nanomicelles formed by sharp-contrast Janus star polymers derived from β-cyclodextrin grafted with lipids and polyzwitterions","authors":"Miao Zhang , Yuting Wen , Zhongxing Zhang , Xia Song , Jingling Zhu , Chitinart Thedrattanawong , Hongzhen Bai , Guping Tang , Kazushi Ogata , Shin-ichi Yusa , Jun Li","doi":"10.1016/j.nantod.2024.102511","DOIUrl":"10.1016/j.nantod.2024.102511","url":null,"abstract":"<div><div>Amphiphilic block polymers have the ability to self-assemble and form nanomicelles, which have been extensively studied as nanocarriers for improving the bioavailability and biodistribution of chemotherapeutic drugs while reducing systemic toxicity. However, polymer micelles often face issues with poor stability in the bloodstream, leading to a short circulation time and leakage of the payload. Here, this work reports a rational design of a sharp-contrast Janus star polymer (SJSP) consisting of multiple arms of superhydrophobic lipid moieties and superhydrophilic polyzwitterion chains attached to a β-cyclodextrin core. The SJSP polymer forms nanomicelles possessing a stable core and a controllable and dense stealth shell that effectively protects them in the bloodstream, preventing payload leakage and blood protein adsorption. It is demonstrated that the hydrophobic/hydrophilic balance can be optimized to achieve strong micellar assembly by adjusting the number of lipid and polyzwitterion arms. The SJSP micelle system shows significantly longer blood circulation time <em>in vivo</em> compared to linear counterparts and other available amphiphilic block copolymer micelle systems. Therefore, the SJSP micelle design offers a promising strategy for developing nanocarriers with potential for translational applications <em>in vivo</em>.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102511"},"PeriodicalIF":13.2,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421447","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 : 2024-10-01DOI: 10.1016/j.nantod.2024.102515
Li Gao , Zhuoyao Shen , Wensheng Xu , Jiang Liu , Qinglong Jia , Chenyang Jin , Ligong Chen , Bowei Wang
Multi-color long-wavelength organic afterglow materials are of great significance in anti-counterfeiting, but their preparation is still challenging. In this paper, a series of room temperature phosphorescence (RTP) films were constructed with polyvinyl alcohol (PVA) as rigid matrix and 9,10-diaminophenanthrene (DAphe) as guest molecule. Surprisingly, by adjusting the doping content of DAphe, their RTP emission peak width could be adjusted accordingly, and the lifetime was up to 3.25 s. Their dopant content dependent and excitation wavelength dependent luminescence characteristics and theoretical calculation results indicated that the observed broad emission peaks of RTP might be attributed to multiple luminescence centers generated by the aggregation of guest molecules. Interestingly, by doping several suitable fluorescent dyes screened as energy acceptors, multi-color, long-lasting afterglow composite films from blue to red were obtained, achieving 0.42 s delayed fluorescence at 661 nm with a fluorescence quantum yield of 32.22 %. In addition, these adjustable afterglow materials had good molding processability, so several cryptographic patterns were achieved to demonstrate their good application prospects in advanced anti-counterfeiting technologies.
{"title":"Ternary composite fluorescent films with tunable color and long lifetime based on efficient TS-FRET","authors":"Li Gao , Zhuoyao Shen , Wensheng Xu , Jiang Liu , Qinglong Jia , Chenyang Jin , Ligong Chen , Bowei Wang","doi":"10.1016/j.nantod.2024.102515","DOIUrl":"10.1016/j.nantod.2024.102515","url":null,"abstract":"<div><div>Multi-color long-wavelength organic afterglow materials are of great significance in anti-counterfeiting, but their preparation is still challenging. In this paper, a series of room temperature phosphorescence (RTP) films were constructed with polyvinyl alcohol (PVA) as rigid matrix and 9,10-diaminophenanthrene (DAphe) as guest molecule. Surprisingly, by adjusting the doping content of DAphe, their RTP emission peak width could be adjusted accordingly, and the lifetime was up to 3.25 s. Their dopant content dependent and excitation wavelength dependent luminescence characteristics and theoretical calculation results indicated that the observed broad emission peaks of RTP might be attributed to multiple luminescence centers generated by the aggregation of guest molecules. Interestingly, by doping several suitable fluorescent dyes screened as energy acceptors, multi-color, long-lasting afterglow composite films from blue to red were obtained, achieving 0.42 s delayed fluorescence at 661 nm with a fluorescence quantum yield of 32.22 %. In addition, these adjustable afterglow materials had good molding processability, so several cryptographic patterns were achieved to demonstrate their good application prospects in advanced anti-counterfeiting technologies.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102515"},"PeriodicalIF":13.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421446","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 : 2024-10-01DOI: 10.1016/j.nantod.2024.102509
Jin Woong Lee , Kwangok P. Nickel , Rachel L. Minne , Justin J. Jeffery , Eduardo Aluicio-Sarduy , Carter Kim , DaWon Kim , Piper A. Rawding , Michael J. Poellmann , Narsimha Mamidi , Jonathan W. Engle , Jung Heon Lee , Hansoo Park , Reinier Hernandez , Randall J. Kimple , Andrew M. Baschnagel , Seungpyo Hong
The Mesenchymal Epithelial Transition (MET) receptor tyrosine kinase is frequently upregulated or mutated in various cancers. Targeting MET signaling pathway has been utilized as a treatment for cancer, since MET overexpression is often associated with poor prognosis. Selective imaging of MET-overexpressing tumor cells would thus provide a high diagnostic value; however, it remains elusive due to a lack of targeted imaging contrast agents. Herein, we have developed a multifunctional diagnostic dendrimer-peptide conjugate (DPC) system with a strong avidity to MET-expressing cancer cells. The system was prepared by conjugating MET-inhibiting peptides (C7) to generation 7 (G7) poly(amidoamine) (PAMAM) dendrimers. Due to the dendrimer-mediated multivalent binding effect, the DPCs exhibited a significantly stronger binding to the human MET protein than free C7, as measured using surface plasmon resonance. Confocal microscopy revealed increased binding of the DPCs to the MET-expressing EBC-1 and UW-Lung-21 cells, whereas a MET knock-out cell line showed negligible interactions with the DPCs. The DPCs were then conjugated with Zirconium-89 for positron emission tomography and computed tomography (PET/CT) scanning, demonstrating their selective accumulation to MET-expressing tumors in vivo. Additionally, the plasma half-life of the DPCs was measured at ∼53 hours, which was significantly longer than free C7. These results collectively suggest that this DPC system has potential as a targeted imaging platform specific to MET-expressing tumors, which would be applicable to various cancer types.
间充质上皮转化（MET）受体酪氨酸激酶经常在各种癌症中上调或突变。靶向 MET 信号通路已被用作癌症的治疗手段，因为 MET 过表达通常与预后不良有关。因此，对 MET 过表达的肿瘤细胞进行选择性成像将具有很高的诊断价值；然而，由于缺乏有针对性的成像造影剂，这一目标仍难以实现。在此，我们开发了一种多功能诊断树枝状聚合物-肽共轭物（DPC）系统，该系统对表达 MET 的肿瘤细胞具有很强的亲和力。该系统是通过将 MET 抑制肽（C7）与第 7 代（G7）聚酰胺胺（PAMAM）树枝状聚合物共轭制备而成的。由于树枝状聚合物介导的多价结合效应，通过表面等离子共振测量，DPCs 与人类 MET 蛋白的结合力明显强于游离 C7。共聚焦显微镜显示，DPCs 与表达 MET 的 EBC-1 和 UW-Lung-21 细胞的结合力增强，而 MET 基因敲除细胞系与 DPCs 的相互作用微乎其微。然后将 DPCs 与锆-89 共轭，用于正电子发射断层扫描和计算机断层扫描（PET/CT），结果表明它们在体内可选择性地聚集到表达 MET 的肿瘤上。此外，DPCs 的血浆半衰期为 53 小时，明显长于游离 C7。这些结果共同表明，这种DPC系统有可能成为特异于MET表达肿瘤的靶向成像平台，适用于各种癌症类型。
{"title":"Multifunctional dendrimer-peptide conjugates for MET receptor-specific imaging of cancer cells","authors":"Jin Woong Lee , Kwangok P. Nickel , Rachel L. Minne , Justin J. Jeffery , Eduardo Aluicio-Sarduy , Carter Kim , DaWon Kim , Piper A. Rawding , Michael J. Poellmann , Narsimha Mamidi , Jonathan W. Engle , Jung Heon Lee , Hansoo Park , Reinier Hernandez , Randall J. Kimple , Andrew M. Baschnagel , Seungpyo Hong","doi":"10.1016/j.nantod.2024.102509","DOIUrl":"10.1016/j.nantod.2024.102509","url":null,"abstract":"<div><div>The Mesenchymal Epithelial Transition (MET) receptor tyrosine kinase is frequently upregulated or mutated in various cancers. Targeting MET signaling pathway has been utilized as a treatment for cancer, since MET overexpression is often associated with poor prognosis. Selective imaging of MET-overexpressing tumor cells would thus provide a high diagnostic value; however, it remains elusive due to a lack of targeted imaging contrast agents. Herein, we have developed a multifunctional diagnostic dendrimer-peptide conjugate (DPC) system with a strong avidity to MET-expressing cancer cells. The system was prepared by conjugating MET-inhibiting peptides (C7) to generation 7 (G7) poly(amidoamine) (PAMAM) dendrimers. Due to the dendrimer-mediated multivalent binding effect, the DPCs exhibited a significantly stronger binding to the human MET protein than free C7, as measured using surface plasmon resonance. Confocal microscopy revealed increased binding of the DPCs to the MET-expressing EBC-1 and UW-Lung-21 cells, whereas a MET knock-out cell line showed negligible interactions with the DPCs. The DPCs were then conjugated with Zirconium-89 for positron emission tomography and computed tomography (PET/CT) scanning, demonstrating their selective accumulation to MET-expressing tumors <em>in vivo</em>. Additionally, the plasma half-life of the DPCs was measured at ∼53 hours, which was significantly longer than free C7. These results collectively suggest that this DPC system has potential as a targeted imaging platform specific to MET-expressing tumors, which would be applicable to various cancer types.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102509"},"PeriodicalIF":13.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356901","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 : 2024-09-28DOI: 10.1016/j.nantod.2024.102512
Keying Chen , Chunxiong Zheng , Yunjuan Lv , Pengkai Zhao , Tong Lin , Yanteng Xu , Huimin Kong , Ke Yi , Qingguo Zhong , Mingqiang Li , Yu Tao , Haixia Wang
In acute inflammation, the heightened activation and recruitment of immune cells present an opportunity to leverage them as natural carriers for efficient transport of diagnostic probes and nanotherapeutics. Although complement opsonization facilitates the internalization of nanomedicines by activated neutrophils, the development of strategies to specifically augment complement deposition remains a challenge. Herein, we engineer silymarin-loaded liposomes (Lips) coated with immunoglobulin G (IgG) to enhance complement 3 (C3) deposition in the protein corona, thereby enabling neutrophil-mediated, precise targeting to the site of inflammation. Through the examination of various serum proteins, we discover that IgG adsorption, particularly with its Fc portion exposed, prominently promotes C3 enrichment in the protein corona, resulting in C3 cleavage into iC3b. This facilitates the uptake of C3-enriched Lips by activated neutrophils with elevated C3 receptor expression, thus improving the efficiency and specificity of nanomedicine delivery to inflammatory site. Following the formation of neutrophil extracellular traps, the released nanomedicine effectively mitigates hepatocyte damage by eliminating accumulated reactive oxygen species and inducing a shift in macrophage polarization towards the anti-inflammatory M2 phenotype. Our IgG-modified nanomedicine demonstrates significant therapeutic efficacy against acute liver failure by regulating the protein corona and hitchhiking neutrophils, offering a promising strategy for efficient and precise treatment of inflammation.
{"title":"Complement opsonized protein corona activated by precoated immunoglobulin enables neutrophil-hitchhiking for rapid and enhanced drug delivery for acute liver failure recovery","authors":"Keying Chen , Chunxiong Zheng , Yunjuan Lv , Pengkai Zhao , Tong Lin , Yanteng Xu , Huimin Kong , Ke Yi , Qingguo Zhong , Mingqiang Li , Yu Tao , Haixia Wang","doi":"10.1016/j.nantod.2024.102512","DOIUrl":"10.1016/j.nantod.2024.102512","url":null,"abstract":"<div><div>In acute inflammation, the heightened activation and recruitment of immune cells present an opportunity to leverage them as natural carriers for efficient transport of diagnostic probes and nanotherapeutics. Although complement opsonization facilitates the internalization of nanomedicines by activated neutrophils, the development of strategies to specifically augment complement deposition remains a challenge. Herein, we engineer silymarin-loaded liposomes (Lips) coated with immunoglobulin G (IgG) to enhance complement 3 (C3) deposition in the protein corona, thereby enabling neutrophil-mediated, precise targeting to the site of inflammation. Through the examination of various serum proteins, we discover that IgG adsorption, particularly with its Fc portion exposed, prominently promotes C3 enrichment in the protein corona, resulting in C3 cleavage into iC3b. This facilitates the uptake of C3-enriched Lips by activated neutrophils with elevated C3 receptor expression, thus improving the efficiency and specificity of nanomedicine delivery to inflammatory site. Following the formation of neutrophil extracellular traps, the released nanomedicine effectively mitigates hepatocyte damage by eliminating accumulated reactive oxygen species and inducing a shift in macrophage polarization towards the anti-inflammatory M2 phenotype. Our IgG-modified nanomedicine demonstrates significant therapeutic efficacy against acute liver failure by regulating the protein corona and hitchhiking neutrophils, offering a promising strategy for efficient and precise treatment of inflammation.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102512"},"PeriodicalIF":13.2,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356898","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 : 2024-09-28DOI: 10.1016/j.nantod.2024.102514
Jiawei Yang , Hao Gu , Yuhui Zhu , Jiaojiao Shao , Haishuang Chang , Mingliang Zhou , Jie Wang , Xinquan Jiang
Reactive oxygen species (ROS) scavenging is essential for periodontal regeneration. However, the dynamic change of the applied materials within the ROS-rich environment and the residual oxidation products in the host highly impact periodontal regeneration. This study successfully constructs a bioreaction system via thiol-ene click chemistry, leveraging the high affinity of glutathione (GSH) for ROS to attract excess ROS to the crosslinking points. Two minutes after hydrogen peroxide (H2O2) treatment, the ROS level in the G8–0 hydrogel acutely decreases, reaching a 4.4 % reduction within 10 minutes, confirming the ROS-trapping efficacy. Through a ‘bait switch-on’ mechanism, hexagonal boron nitride (hBN) takes over the captured ROS and the oxidation products of pectin further drive the reduction reaction, ultimately restoring the extracellular environment. The self-cascade products, oxidized hBN, reshape the intracellular oxidative stress (OS) environment, achieving a synergistic extra- and intra-cellular treatment. The significantly high reduced to oxidized glutathione (GSH/GSSG) ratio in G8–10 hydrogel (∼80 %) illustrates a reversal of oxidative stress in bone marrow stem cells (BMSCs). On a molecular level, the bioreaction system inhibits the NF-κB pathway, promoting the expression of key antioxidant genes (Nqo1 and Nrf2) and osteogenic molecules (ALP and OCN), thereby reversing the detrimental effects of OS on BMSCs. In vivo application demonstrated the system’s strong redox-balancing and osteogenic capabilities in the periodontal inflammation environment. This novel antioxidant bioreaction system, characterized by self-cascade ROS-trapping and product utilization, offers innovative treatment strategies for tissue regeneration under conditions of excessive OS.
{"title":"Self-cascade ROS-trapping bioreaction system reverses stem cell oxidative stress fate for osteogenesis","authors":"Jiawei Yang , Hao Gu , Yuhui Zhu , Jiaojiao Shao , Haishuang Chang , Mingliang Zhou , Jie Wang , Xinquan Jiang","doi":"10.1016/j.nantod.2024.102514","DOIUrl":"10.1016/j.nantod.2024.102514","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) scavenging is essential for periodontal regeneration. However, the dynamic change of the applied materials within the ROS-rich environment and the residual oxidation products in the host highly impact periodontal regeneration. This study successfully constructs a bioreaction system via thiol-ene click chemistry, leveraging the high affinity of glutathione (GSH) for ROS to attract excess ROS to the crosslinking points. Two minutes after hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) treatment, the ROS level in the G8–0 hydrogel acutely decreases, reaching a 4.4 % reduction within 10 minutes, confirming the ROS-trapping efficacy. Through a ‘bait switch-on’ mechanism, hexagonal boron nitride (hBN) takes over the captured ROS and the oxidation products of pectin further drive the reduction reaction, ultimately restoring the extracellular environment. The self-cascade products, oxidized hBN, reshape the intracellular oxidative stress (OS) environment, achieving a synergistic extra- and intra-cellular treatment. The significantly high reduced to oxidized glutathione (GSH/GSSG) ratio in G8–10 hydrogel (∼80 %) illustrates a reversal of oxidative stress in bone marrow stem cells (BMSCs). On a molecular level, the bioreaction system inhibits the NF-κB pathway, promoting the expression of key antioxidant genes (<em>Nqo1</em> and <em>Nrf2</em>) and osteogenic molecules (ALP and OCN), thereby reversing the detrimental effects of OS on BMSCs. In vivo application demonstrated the system’s strong redox-balancing and osteogenic capabilities in the periodontal inflammation environment. This novel antioxidant bioreaction system, characterized by self-cascade ROS-trapping and product utilization, offers innovative treatment strategies for tissue regeneration under conditions of excessive OS.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102514"},"PeriodicalIF":13.2,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327243","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}
Pub Date : 2024-09-27DOI: 10.1016/j.nantod.2024.102508
Nier Wu , Shengnan Fu , Chenxi Dai , Lingfei Hu , Jiaxin Li , Fangzhou Chen , Lin Wang , Xin Su , Dongsheng Zhou
Antimicrobial peptides (AMPs) represent a good alternative for treating infections to overcome increasing antibiotic resistance problems. DNA nanostructures have been utilized as the delivery carrier of AMPs to enhance their performance, but mechanisms of action remain largely unclear. In this work, DNA nanotube (DNT) was chosen as a preferred carrier of AMPs owing to its high binding affinity and loading capacity, and an engineered broad-spectrum AMP named RP557 was screened as the cargo though molecular simulation and subsequent loading experiments. RP557 molecules were then loaded onto DNT through electrostatic interaction to construct RP557@DNT nanocomplex for improved anti-infective therapy. Loaded RP557 possessed the lower cytotoxicity to fibroblasts and epithelial cells and the higher compatibility to red blood cells relative to free RP557 in vitro, and RP557@DNT displayed the highly favored biodegradability and biosafety at the animal level. In addition, compared to free RP557, RP557@DNT endowed better bactericidal activity in vitro and in vivo because loaded RP557 exhibited higher resistance to serum protease degradation and controlled release onto bacterial cell membrane. The high therapeutic effect of RP557@DNT primarily depended on the acceleration of inflammation resolution (involving the reduction in proinflammatory factor production, innate immune cell recruitment, and adaptive immunity) and tissue repair (involving the up-regulation of multiple epidermal and dermal repair pathways). In summary, RP557@DNT showed significantly enhanced anti-enzymolysis, antibacterial activity, and biosafety relative to free RP557, and thus it represented a high-efficiency antibiotics-alternative strategy for treating refractory infections.
{"title":"DNA nanotube-carrying antimicrobial peptide confers improved anti-infective therapy","authors":"Nier Wu , Shengnan Fu , Chenxi Dai , Lingfei Hu , Jiaxin Li , Fangzhou Chen , Lin Wang , Xin Su , Dongsheng Zhou","doi":"10.1016/j.nantod.2024.102508","DOIUrl":"10.1016/j.nantod.2024.102508","url":null,"abstract":"<div><div>Antimicrobial peptides (AMPs) represent a good alternative for treating infections to overcome increasing antibiotic resistance problems. DNA nanostructures have been utilized as the delivery carrier of AMPs to enhance their performance, but mechanisms of action remain largely unclear. In this work, DNA nanotube (DNT) was chosen as a preferred carrier of AMPs owing to its high binding affinity and loading capacity, and an engineered broad-spectrum AMP named RP557 was screened as the cargo though molecular simulation and subsequent loading experiments. RP557 molecules were then loaded onto DNT through electrostatic interaction to construct RP557@DNT nanocomplex for improved anti-infective therapy. Loaded RP557 possessed the lower cytotoxicity to fibroblasts and epithelial cells and the higher compatibility to red blood cells relative to free RP557 <em>in vitro</em>, and RP557@DNT displayed the highly favored biodegradability and biosafety at the animal level. In addition, compared to free RP557, RP557@DNT endowed better bactericidal activity <em>in vitro</em> and <em>in vivo</em> because loaded RP557 exhibited higher resistance to serum protease degradation and controlled release onto bacterial cell membrane. The high therapeutic effect of RP557@DNT primarily depended on the acceleration of inflammation resolution (involving the reduction in proinflammatory factor production, innate immune cell recruitment, and adaptive immunity) and tissue repair (involving the up-regulation of multiple epidermal and dermal repair pathways). In summary, RP557@DNT showed significantly enhanced anti-enzymolysis, antibacterial activity, and biosafety relative to free RP557, and thus it represented a high-efficiency antibiotics-alternative strategy for treating refractory infections.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102508"},"PeriodicalIF":13.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324143","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 : 2024-09-26DOI: 10.1016/j.nantod.2024.102510
You Zhang , Xiaofeng Wang , Shu Liu , Jing Wang , Pingping Zheng , Damin Xu , Qian Liu , Liming Wang , Wenhong Fan , Fengchang Wu
As novel antioxidants, hydrogen nanobubbles (NBs) intricately regulate the growth and developmental processes of organisms, bolstering their tolerance to external stresses. Despite their recognized potential, the precise antioxidative mechanisms remain inadequately elucidated. In this study, we present evidence supporting the protective role of hydrogen NBs in an oxidative stress system, utilizing Cu2+ as a prototypical inducer and Tetrahymena thermophila as a representative model organism. To elucidate the molecular mechanism of this phenomenon, we employed a comprehensive approach, integrating transcriptomic analysis and molecular dynamics simulations. Additionally, intrinsic differential scanning and surface plasmon resonance techniques were applied to unveil the molecular-level response and nanoscale interactions. Our investigation revealed that hydrogen NBs induce a notable upregulation in the expression of glutathione peroxidase (GPx). Moreover, compared to molecular hydrogen, hydrogen NBs have a more pronounced effect on the structural reconfiguration and catalytic efficacy of GPx, as demonstrated by the greater reduction in the distance between the catalytic center amino acids and a significant increase in GPx’s affinity for GSH. In summary, our findings underscore GPx as the targeted molecules through which hydrogen NBs exert their antioxidative effects. These insights contribute to a deeper comprehension of the molecular implications of hydrogen NBs and provide new perspectives for alleviating the toxicity of environmental pollutants.
作为一种新型抗氧化剂，纳米氢气泡（NBs）能错综复杂地调节生物体的生长和发育过程，增强其对外部压力的耐受力。尽管氢纳米气泡具有公认的潜力，但其确切的抗氧化机制仍未得到充分阐明。在本研究中，我们以 Cu2+ 为典型诱导剂，以嗜热四膜虫为代表性模式生物，提出了支持氢 NBs 在氧化应激系统中发挥保护作用的证据。为了阐明这一现象的分子机制，我们采用了一种综合方法，将转录组分析和分子动力学模拟结合起来。此外，我们还采用了本征差分扫描和表面等离子体共振技术来揭示分子级响应和纳米级相互作用。我们的研究发现，氢气 NB 可诱导谷胱甘肽过氧化物酶（GPx）的表达显著上调。此外，与分子氢相比，氢 NB 对 GPx 的结构重构和催化功效有更明显的影响，这表现在催化中心氨基酸之间的距离更小，GPx 对 GSH 的亲和力显著增加。总之，我们的研究结果表明，GPx 是氢核苷酸发挥抗氧化作用的目标分子。这些发现有助于加深对氢核糖分子意义的理解，并为减轻环境污染物的毒性提供了新的视角。
{"title":"Hydrogen nanobubbles enhancing antioxidant activity of glutathione peroxidase: Superiority at the nanoscale over molecular scale","authors":"You Zhang , Xiaofeng Wang , Shu Liu , Jing Wang , Pingping Zheng , Damin Xu , Qian Liu , Liming Wang , Wenhong Fan , Fengchang Wu","doi":"10.1016/j.nantod.2024.102510","DOIUrl":"10.1016/j.nantod.2024.102510","url":null,"abstract":"<div><div>As novel antioxidants, hydrogen nanobubbles (NBs) intricately regulate the growth and developmental processes of organisms, bolstering their tolerance to external stresses. Despite their recognized potential, the precise antioxidative mechanisms remain inadequately elucidated. In this study, we present evidence supporting the protective role of hydrogen NBs in an oxidative stress system, utilizing Cu<sup>2+</sup> as a prototypical inducer and <em>Tetrahymena thermophila</em> as a representative model organism. To elucidate the molecular mechanism of this phenomenon, we employed a comprehensive approach, integrating transcriptomic analysis and molecular dynamics simulations. Additionally, intrinsic differential scanning and surface plasmon resonance techniques were applied to unveil the molecular-level response and nanoscale interactions. Our investigation revealed that hydrogen NBs induce a notable upregulation in the expression of glutathione peroxidase (GPx). Moreover, compared to molecular hydrogen, hydrogen NBs have a more pronounced effect on the structural reconfiguration and catalytic efficacy of GPx, as demonstrated by the greater reduction in the distance between the catalytic center amino acids and a significant increase in GPx’s affinity for GSH. In summary, our findings underscore GPx as the targeted molecules through which hydrogen NBs exert their antioxidative effects. These insights contribute to a deeper comprehension of the molecular implications of hydrogen NBs and provide new perspectives for alleviating the toxicity of environmental pollutants.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102510"},"PeriodicalIF":13.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324138","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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