Multiplexed Aptamer-Lattice Nanodevice for One-Step Phenotyping and Functional Quality Control of CAR-T Cells.

IF 9.1 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Letters Pub Date : 2025-09-29 DOI:10.1021/acs.nanolett.5c03452

Meixia Wang, Zhu Li, Yangbing Li, Yangguang Zhao, Miao Wang, Junyu Liao, Zhiyang Yuwen, Pengfei Liu, Fang He, Xiaoxiao Han, Li Zhu, Ping Wei, Na Cai, Zhou Nie, Hong-Hui Wang

{"title":"Multiplexed Aptamer-Lattice Nanodevice for One-Step Phenotyping and Functional Quality Control of CAR-T Cells.","authors":"Meixia Wang, Zhu Li, Yangbing Li, Yangguang Zhao, Miao Wang, Junyu Liao, Zhiyang Yuwen, Pengfei Liu, Fang He, Xiaoxiao Han, Li Zhu, Ping Wei, Na Cai, Zhou Nie, Hong-Hui Wang","doi":"10.1021/acs.nanolett.5c03452","DOIUrl":null,"url":null,"abstract":"<p><p>Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized cancer treatment but continues to face substantial quality control challenges due to cellular heterogeneity. Here, we report a multiplexed nanodevice, the Aptamer Lattice-Powered Hybrid Architecture (ALPHA), for one-step phenotypic and functional analysis of CAR-T cells. By integrating aptamers targeting CD3, CD25, and CD122 into a programmable DNA lattice scaffold, ALPHA enables rapid, wash-free, and orthogonal fluorescence activation. Within 30 min, the platform distinguishes resting from activated T cells and generates an Activation Index that strongly correlates with cytokine secretion and cytotoxic function. To directly monitor cytotoxicity, an integrated ATP-responsive aptamer detects extracellular ATP released from lysed targets, enabling real-time assessment of target cell killing. ALPHA also captured donor-dependent functional variability in CAR-T samples, consistent with conventional functional readouts. Overall, ALPHA represents a versatile and scalable tool for comprehensive quality control of engineered immune cells during manufacturing.</p>","PeriodicalId":53,"journal":{"name":"Nano Letters","volume":" ","pages":""},"PeriodicalIF":9.1000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nano Letters","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1021/acs.nanolett.5c03452","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}

引用次数: 0

Abstract

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized cancer treatment but continues to face substantial quality control challenges due to cellular heterogeneity. Here, we report a multiplexed nanodevice, the Aptamer Lattice-Powered Hybrid Architecture (ALPHA), for one-step phenotypic and functional analysis of CAR-T cells. By integrating aptamers targeting CD3, CD25, and CD122 into a programmable DNA lattice scaffold, ALPHA enables rapid, wash-free, and orthogonal fluorescence activation. Within 30 min, the platform distinguishes resting from activated T cells and generates an Activation Index that strongly correlates with cytokine secretion and cytotoxic function. To directly monitor cytotoxicity, an integrated ATP-responsive aptamer detects extracellular ATP released from lysed targets, enabling real-time assessment of target cell killing. ALPHA also captured donor-dependent functional variability in CAR-T samples, consistent with conventional functional readouts. Overall, ALPHA represents a versatile and scalable tool for comprehensive quality control of engineered immune cells during manufacturing.

Abstract Image

查看原文本刊更多论文

用于CAR-T细胞一步表型和功能质量控制的多路适配体-晶格纳米器件。

嵌合抗原受体T （CAR-T）细胞疗法已经彻底改变了癌症治疗，但由于细胞异质性，仍然面临着重大的质量控制挑战。在这里，我们报道了一种用于CAR-T细胞一步表型和功能分析的多路复用纳米器件，适体晶格动力混合结构（ALPHA）。通过将靶向CD3、CD25和CD122的适体整合到可编程的DNA晶格支架中，ALPHA实现了快速、无洗涤和正交的荧光激活。在30分钟内，该平台将静止T细胞与活化T细胞区分开来，并生成与细胞因子分泌和细胞毒功能密切相关的激活指数。为了直接监测细胞毒性，一个集成的ATP响应适体可以检测裂解靶标释放的细胞外ATP，从而实时评估靶细胞的杀伤情况。ALPHA还捕获了CAR-T样本中供体依赖的功能变异性，与传统的功能读数一致。总的来说，ALPHA代表了一个多功能和可扩展的工具，用于在制造过程中对工程免疫细胞进行全面的质量控制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nano Letters 工程技术-材料科学：综合

CiteScore

16.80

自引率

2.80%

发文量

1182

审稿时长

1.4 months

期刊介绍： Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.