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Three-dimensional magnetophoretic bioassay based on artificial intelligence-mediated load assignment for the femtomolar and washing-free detection of analytes 基于人工智能负载分配的三维磁泳生物分析法,用于飞摩尔和免清洗分析物检测
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-16 DOI: 10.1016/j.nantod.2024.102522
Ting Xiao , Weiqi Zhao , Minjie Han , Xiaolin Huang , Ben Zhong Tang , Yiping Chen
The quantification of low-abundance biomarkers or trace harmful substances in complex samples at femtomolar-level sensitivity requires labor-intensive incubation and multiwashing steps. Herein, we explore a trajectory/accumulation/color three-dimensional microfluidic magnetophoresis immunoassay (TAC-MMI) based on an artificial intelligence (AI)-assisted load assignment strategy, enabling washing-free and femtomolar detection of interleukin-6 in serum samples and chloramphenicol in food samples within 30 min. The biorecognition between targets and biometric molecules (antigens and antibodies) immobilized on magnetic nanoparticles (MNPs) and polystyrene microsphere-horseradish peroxidase (PM-HRP) conjugate induces MNP-target-PM-HRP immunocomplexes with different magnetic contents, where the concentration of targets is transformed into spatial visualization information through magnetophoretic force using a linear microtube array within a microfluidic chip. The visualization information can be enhanced by the HRP-catalyzed color reaction. Trajectory-accumulation-color of PM in each microtube is precisely assigned significance and identified via AI for bioanalysis. TAC-MMI demonstrates high sensitivity (fM level), rapidity (30 min), and ease of use without washing steps. The three-dimensional sensing strategy based on load-assignment improved sensitivity by more than 96-fold compared with the traditional one-dimensional sensing strategy. Compared to chemiluminescence immunoassay (CLIA), TAC-MMI achieved 15-fold improvement in sensitivity in only one-third of the time required for CLIA, suggesting a promising magnetophoretic bioassay for diagnostic technology.
要以飞摩尔级的灵敏度定量复杂样品中的低丰度生物标记物或痕量有害物质,需要耗费大量人力的孵育和多次洗涤步骤。在此,我们探索了一种基于人工智能(AI)辅助负载分配策略的轨迹/累积/颜色三维微流控磁泳免疫分析法(TAC-MMI),可在 30 分钟内免洗、飞摩尔级地检测血清样品中的白细胞介素-6 和食品样品中的氯霉素。固定在磁性纳米颗粒(MNPs)和聚苯乙烯微球-辣根过氧化物酶(PM-HRP)共轭物上的目标物和生物识别分子(抗原和抗体)之间的生物识别诱导了不同磁性含量的 MNP-目标物-PM-HRP 免疫复合物,目标物的浓度通过微流控芯片内的线性微管阵列的磁导力转化为空间可视化信息。可视化信息可通过 HRP 催化的颜色反应得到增强。每个微管中可吸入颗粒物的轨迹-累积-颜色都被精确地赋予了意义,并通过人工智能进行生物分析识别。TAC-MMI 具有高灵敏度(fM 级)、快速(30 分钟)和使用方便等特点,无需清洗步骤。与传统的一维传感策略相比,基于负载分配的三维传感策略将灵敏度提高了 96 倍以上。与化学发光免疫测定(CLIA)相比,TAC-MMI 的灵敏度提高了 15 倍,所需的时间仅为 CLIA 的三分之一,这表明磁浮生物测定诊断技术前景广阔。
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引用次数: 0
In vivo engineering chimeric antigen receptor immune cells with emerging nanotechnologies 利用新兴纳米技术在体内制造嵌合抗原受体免疫细胞
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-10 DOI: 10.1016/j.nantod.2024.102517
Hui Ren , Yuzhi Jin , Huanhuan Huang , Wei Wu , Xiaomeng Dai , Weijia Fang , Jing Qin , Hongjun Li , Peng Zhao
Adoptive cell therapy with chimeric antigen receptor (CAR) has revolutionized cancer treatment in the past decade. Now several adoptive cell therapies are approved, and researchers are extending the application of adoptive cell therapy beyond oncology, such as autoimmune diseases, inherited blood disorders, infectious diseases and fibrosis. Evidence from clinical studies underscores the potential of cell therapy in cancer and noncancerous conditions. However, conventional manufacture of adoptive CAR-cell ex vivo is time-consuming and expensive in which immune cells are extracted from the patients, engineered to target cancer cells and reinjected to the body. The ways to produce CAR-cell in the body, as a promising alternative, may make the awfully expensive and personalized cell therapy more accessible. Here, we thoroughly summarize the current state of clinical trials on adoptive cell therapy, representing by CAR-T, CAR-nature killer cell (CAR-NK) and CAR-Macrophage (CAR-M), and highlight the latest advances in off-the-shelf nanocarrier- and virus-based in vivo CAR cargo delivery strategies, and corresponding precision targeting strategies, to provide a future perspective regarding in vivo engineering CAR-cell.
过去十年间,采用嵌合抗原受体(CAR)的收养细胞疗法彻底改变了癌症治疗。现在,多种采用性细胞疗法已获得批准,研究人员正在将采用性细胞疗法的应用范围扩展到肿瘤以外的领域,如自身免疫性疾病、遗传性血液病、传染性疾病和纤维化。临床研究的证据强调了细胞疗法在癌症和非癌症疾病中的潜力。然而,传统的体外 CAR 细胞制造既耗时又昂贵,需要从患者体内提取免疫细胞,设计成针对癌细胞的细胞,然后再注射到体内。在体内制造 CAR 细胞的方法是一种很有前景的替代方法,它可以使昂贵的个性化细胞疗法变得更容易获得。在此,我们全面总结了以CAR-T、CAR-自然杀伤细胞(CAR-NK)和CAR-巨噬细胞(CAR-M)为代表的采用性细胞疗法的临床试验现状,并重点介绍了基于现成纳米载体和病毒的体内CAR货物递送策略以及相应的精准靶向策略的最新进展,以提供有关体内工程CAR-细胞的未来展望。
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引用次数: 0
Biomimetic nanoreactor of catalase and nitric oxide enhance peroxynitrite generation for radiosensitization 过氧化氢酶和一氧化氮的仿生纳米反应器可增强过氧化亚硝酸盐的生成,从而提高辐射敏感性
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-07 DOI: 10.1016/j.nantod.2024.102519
Yao Wu , Yongping Li , Honglei Xie , Yichen Zhang , Xinyue Bao , Xianyi Sha , Jingyuan Wen , Yaping Li , Zhiwen Zhang
The redundant DNA-repairing capacity and robust hypoxia in tumors pose significant challenges of cancer radiotherapy. Herein, an amphiphilic nitric oxide (NO)-supplying conjugate (PEG−SMA−NO) was synthesized and integrated with oxygen-producing catalase (CAT) to fabricate a biomimetic nanoreactor (termed as CAT@PNN), aiming to enhance peroxynitrite generation upon X-ray radiation for radiosensitization. CAT@PNN effectively reduced the hypoxic levels and produced abundant NO molecules in tumors. Upon X-ray radiation, excessive peroxynitrite radicals were generated with profound spatiotemporal distribution profiles, which effectively downregulated the expression of DNA-repairing RAD51, reduced the proportion of cancer-stem like cells, and enhanced the levels of DNA damages, cell apoptosis and lipid peroxidation to aid radiosensitization. Specifically, the combination of single treatment of CAT@PNN with X-ray radiation resulted in a 95.41 % inhibition of tumor growth and significantly extended survival in 4T1 tumor model. Therefore, the biomimetic nanoreactor of CAT@PNN offers a promising peroxynitrite-generating nanoplatform to enhance radiosensitization in cancer radiotherapy.
肿瘤中冗余的DNA修复能力和强大的缺氧能力给癌症放疗带来了巨大挑战。本文合成了一种两亲性一氧化氮(NO)供应共轭物(PEG-SMA-NO),并将其与产氧过氧化氢酶(CAT)结合,制成了一种仿生纳米反应器(CAT@PNN),旨在增强X射线辐射时过氧亚硝酸盐的生成,从而实现放射增敏。CAT@PNN能有效降低肿瘤的缺氧水平,并产生丰富的NO分子。在X射线照射下,过氧化亚硝酸自由基的生成具有深刻的时空分布特征,可有效下调DNA修复RAD51的表达,降低癌干细胞的比例,并提高DNA损伤、细胞凋亡和脂质过氧化的水平,从而帮助放射增敏。具体而言,在 4T1 肿瘤模型中,将 CAT@PNN 与 X 射线辐射结合使用,可使肿瘤生长抑制率达到 95.41%,并显著延长存活时间。因此,CAT@PNN 的仿生纳米反应器为提高癌症放疗的放射增敏提供了一个前景广阔的过亚硝酸盐生成纳米平台。
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引用次数: 0
Liquid-liquid phase separation in human diseases: Functions, mechanisms and treatments 人类疾病中的液-液相分离:功能、机制和治疗
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-07 DOI: 10.1016/j.nantod.2024.102521
Tongqing Yue , Fei Zhang , Yanan Wei, Zejun Wang
Cells are separated into functional regions by non-membrane organelles and membrane-enclosed organelles, ensuring that various cellular activities occur in a controlled manner in space and time. There is increasing evidence that large numbers of non-membrane compartments, collectively referred to as biomacromolecular condensates or droplets, are formed in cells through liquid-liquid phase separation (LLPS). Phase-separated condensates play a role in numerous biological activities and intracellular spatiotemporal regulation, such as cellular transcription, chromatin maintenance, signal transduction, and immune response. However, abnormal phase separation and transformation are closely linked to many major human diseases. This review comprehensively summarizes the detailed mechanisms of biomacromolecular condensates formation and physiological functions, and discusses the latest progress in elucidating the pathological mechanisms of various human diseases caused by abnormal LLPS and their treatment options.
细胞被非膜细胞器和膜封闭细胞器分隔成功能区,确保各种细胞活动在空间和时间上以受控方式进行。越来越多的证据表明,细胞内通过液-液相分离(LLPS)形成了大量非膜区室,统称为生物分子凝聚体或液滴。相分离的凝聚体在许多生物活动和细胞内时空调节中发挥作用,如细胞转录、染色质维持、信号转导和免疫反应。然而,异常的相分离和转化与许多重大人类疾病密切相关。这篇综述全面总结了生物大分子凝聚物形成的详细机制和生理功能,并探讨了阐明由异常 LLPS 引起的各种人类疾病的病理机制及其治疗方案的最新进展。
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引用次数: 0
MCL1 inhibitor S63845 delivered by follicle-stimulating hormone modified liposome potentiates carboplatin efficacy in ovarian cancer 通过卵泡刺激素修饰脂质体递送的 MCL1 抑制剂 S63845 可增强卡铂对卵巢癌的疗效
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-05 DOI: 10.1016/j.nantod.2024.102513
Yanan Zhang , Qingzhen Wang , Wenxin Li , Xin Li , Yuqing Li , Zhihua Liu , Huige Zhou , Aiping Luo , Chunying Chen , Bin Li
Platinum resistance cause therapeutic failure and poor prognosis in ovarian cancer, and evasion of apoptosis is a critical factor in chemoresistance. A limited number of FDA-approved anticancer drugs directly target apoptotic pathways. Here, we discovered that MCL1, a critical anti-apoptotic protein, is amplified and associated with platinum resistance and survival in ovarian cancer, assisting in personalized treatment. We further identified S63845 through drug-based screening, the most potent MCL1 inhibitor, which efficiently enhanced carboplatin (CBP) sensitivity in various ovarian cancer models, including primary ovarian cancer cells, orthotopic ovarian cancer, peritoneal metastasis, and human patient-derived xenograft (PDX) models. Mechanistically, S63845 competitively binds to MCL1, disrupts the binding of apoptosis effector (BAK and BAX) or pro-apoptotic BH3 protein (BIM) to MCL1 respectively, and eventually enhances CBP-induced apoptosis.To promote the clinical transformation of S63845, we developed follicle-stimulating hormone-modified liposome nanoparticles (S63845@Lipo-FSH) to enhance stability, membrane penetration, and tumor-targeting capabilities. S63845@Lipo-FSH exhibits a superior therapeutic efficacy and tumor targeting compared to free S63845, even when the dose of S63845 is reduced to one-fifth. Overall, targeting MCL1 by S63845@Lipo-FSH enhances CBP efficiency in ovarian cancer, with safety and efficacy, suggesting that this strategy is effective and promising for clinical application.
铂类药物的耐药性会导致卵巢癌治疗失败和预后不良,而细胞凋亡的逃避是导致化疗耐药性的关键因素。美国 FDA 批准的抗癌药物中,直接针对细胞凋亡通路的药物数量有限。在这里,我们发现卵巢癌中关键的抗凋亡蛋白MCL1被扩增,并与铂类药物耐药性和生存率相关,这有助于个性化治疗。我们通过药物筛选进一步确定了 S63845,它是最有效的 MCL1 抑制剂,能有效提高卡铂(CBP)在各种卵巢癌模型中的敏感性,包括原发性卵巢癌细胞、正位卵巢癌、腹膜转移瘤和人类患者来源异种移植(PDX)模型。为促进S63845的临床转化,我们开发了卵泡刺激素修饰的脂质体纳米颗粒(S63845@Lipo-FSH),以增强其稳定性、膜穿透性和肿瘤靶向能力。与游离 S63845 相比,即使 S63845 的剂量减少到五分之一,S63845@脂质-FSH 也能显示出更优越的疗效和肿瘤靶向性。总之,S63845@Lipo-FSH靶向MCL1能提高CBP对卵巢癌的治疗效率,而且安全有效,表明这种策略是有效的,具有临床应用前景。
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引用次数: 0
Supramolecular photothermal agents mediated by black hole hosts 由黑洞宿主介导的超分子光热剂
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-05 DOI: 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.
高性能有机光热剂(PTAs)主要取决于对非辐射衰变过程的操控,这通常需要复杂而耗时的分子工程。主要的挑战在于如何使染料和淬灭剂在亚纳米距离内紧密分子接触,以实现有效淬灭。本文介绍了一种通过非辐射电子转移制造超分子 PTA 的主客策略。通过染料与 "黑洞宿主"--季铵改性钙[4]炔四辛基氧基醚(QC4A-8C)--的强络合,十种不同染料的光热性能得到了前所未有的优化。利用四磺酸锌酞菁@QC4A-8C对超分子 PTA 在生物应用中的光热疗法潜力进行了体外和体内评估。这项研究为利用现有染料通过电子传递增强光热效应提供了见解,为开发安全高效的超分子 PTA 提供了一条简化途径。
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引用次数: 0
Optically active persistent luminescence in supramolecular nanoassemblies constructed from entirely achiral building blocks 完全非手性结构单元构建的超分子纳米组装体中的光学活性持久荧光
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-03 DOI: 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.
光学活性持久发光材料因其独特的发光特性和展现丰富圆偏振信息的能力而备受关注。尽管人们在利用手性分子或聚合物开发圆偏振持久发光(CPPL)材料方面做出了大量努力,但利用非手性单元制造 CPPL 材料仍然是一个巨大的挑战。在这项工作中,我们介绍了一种利用完全非手性有机分子制造 CPPL 材料的高效共组装策略。共组装复合物的光学活性归因于结构的手性,而结构的手性来自于 C3 对称分子自组装过程中对称性破坏时形成的手性纳米螺旋。具有持久磷光的手性分子可通过氢键粘附到这些手性纳米结构上,并在干燥阶段形成沿螺旋纤维排列的纳米晶体,从而产生圆偏振的持久磷光。通过氢键驱动的共组装实现了更高的 CPPL 效率,其范围从蓝色到黄色,不对称系数超过 1.2 × 10-2,室温下的寿命长达 0.6 秒。此外,还利用自制的时间分辨圆偏振长余辉探测平台捕获了这些共组装体的 CPPL 光谱。这项研究不仅为利用非手性构件高效设计 CPPL 材料提供了一种新方法,而且极大地拓宽了实时 CPPL 分析的研究领域,为 CPPL 材料的探索开辟了新天地。
{"title":"Optically active persistent luminescence in supramolecular nanoassemblies constructed from entirely achiral building blocks","authors":"Haolai Mao ,&nbsp;Xue Jin ,&nbsp;Chengxi Li ,&nbsp;Chengyu Jiang ,&nbsp;Xuefeng Yang ,&nbsp;Zhijie Wang ,&nbsp;Da-Wei Fu ,&nbsp;Yi Zhang ,&nbsp;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}
引用次数: 0
In situ engineering of mRNA-CAR T cells using spleen-targeted ionizable lipid nanoparticles to eliminate cancer cells 利用脾脏靶向可离子化脂质纳米颗粒原位工程设计 mRNA-CAR T 细胞,以消灭癌细胞
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-03 DOI: 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)。
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引用次数: 0
Long in vivo circulating nanomicelles formed by sharp-contrast Janus star polymers derived from β-cyclodextrin grafted with lipids and polyzwitterions 由与脂质和聚齐聚糖接枝的β-环糊精衍生的尖锐对比 Janus 星聚合物形成的体内循环纳米长小孔
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-02 DOI: 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.
两亲性嵌段聚合物具有自组装和形成纳米胶束的能力,人们已将其作为纳米载体进行了广泛研究,以改善化疗药物的生物利用度和生物分布,同时降低全身毒性。然而,聚合物胶束往往面临在血液中稳定性差的问题,导致循环时间短和有效载荷泄漏。在此,本研究报告了对一种对比鲜明的 Janus 星聚合物(SJSP)的合理设计,该聚合物由超疏水性脂质分子和超亲水性聚齐聚糖链的多臂组成,并附着在β-环糊精核心上。SJSP 聚合物形成的纳米蜂窝具有稳定的核心和可控的致密隐形外壳,可在血液中有效保护蜂窝,防止有效载荷泄漏和吸附血液蛋白质。研究表明,疏水/亲水平衡可以通过调整脂质和聚齐聚糖臂的数量来优化,从而实现强大的胶束组装。SJSP 胶束系统在体内的血液循环时间明显长于线性系统和其他现有的两亲嵌段共聚物胶束系统。因此,SJSP 胶束设计为开发具有体内转化应用潜力的纳米载体提供了一种前景广阔的策略。
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引用次数: 0
Ternary composite fluorescent films with tunable color and long lifetime based on efficient TS-FRET 基于高效 TS-FRET 的颜色可调、寿命长的三元复合荧光膜
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-01 DOI: 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.
多色长波长有机余辉材料在防伪领域具有重要意义,但其制备仍具有挑战性。本文以聚乙烯醇(PVA)为刚性基体,9,10-二氨基菲(DAphe)为客体分子,构建了一系列室温磷光(RTP)薄膜。令人惊奇的是,通过调整 DAphe 的掺杂含量,其 RTP 发射峰宽度可相应调整,寿命可达 3.25 秒。它们的发光特性与掺杂剂含量和激发波长有关,理论计算的结果表明,观察到的 RTP 宽发射峰可能是由客体分子聚集产生的多个发光中心造成的。有趣的是,通过掺入几种合适的荧光染料作为能量接受体,可获得从蓝色到红色的多色、长效余辉复合薄膜,在 661 纳米波长下可实现 0.42 秒的延迟荧光,荧光量子产率为 32.22%。此外,这些可调余辉材料还具有良好的成型加工性,因此可实现多种密码图案,在先进的防伪技术中具有良好的应用前景。
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引用次数: 0
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