中国科学技术大学刘世勇团队开发出编码聚合物两亲性数字胶束，用于直接序列阅读和体外无标签定量。相关研究成果于2022年11月3日发表在国际顶尖学术期刊《自然—化学》。

复杂生物环境中合成聚合物的识别和定量对于递送、传感和载体功能至关重要，但基于成像探针标记的传统技术只能提供定性结果。

该文中，研究人员报道了精确序列定义的两亲性聚合物的模块化结构，这些聚合物自组装成数字胶束，其轮廓长度由低聚氨基甲酸酯序列严格控制。通过基质辅助激光解吸/电离（MALDI）串联质谱法实现直接序列读取，通过碱金属离子与聚（乙二醇）树突的高亲和力结合，和苄基氨基甲酸酯键的选择性裂解来促进。

体内给药时，可以通过细胞、器官和组织切片水平的MALDI和MALDI成像来识别、序列解码和量化四种类型的数字胶束的混合物，从而能够直接比较同一动物中每种类型的数码胶束的生物学特性。

能够直接测序和高通量无标记定量的数字胶束和编码两亲性的概念，可用于下一代精密纳米药物设计（如数字脂质）和蛋白质电晕研究。

附：英文原文

Title: Digital micelles of encoded polymeric amphiphiles for direct sequence reading and ex vivo label-free quantification

Author: Shi, Qiangqiang, Yin, Hao, Song, Rundi, Xu, Jie, Tan, Jiajia, Zhou, Xin, Cen, Jie, Deng, Zhengyu, Tong, Huimin, Cui, Chenhui, Zhang, Yanfeng, Li, Xiaopeng, Zhang, Zhengbiao, Liu, Shiyong

Issue&Volume: 2022-11-03

Abstract: Identification and quantification of synthetic polymers in complex biological milieu are crucial for delivery, sensing and scaffolding functions, but conventional techniques based on imaging probe labellings only afford qualitative results. Here we report modular construction of precise sequence-defined amphiphilic polymers that self-assemble into digital micelles with contour lengths strictly regulated by oligourethane sequences. Direct sequence reading is accomplished with matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry, facilitated by high-affinity binding of alkali metal ions with poly(ethylene glycol) dendrons and selective cleavage of benzyl-carbamate linkages. A mixture of four types of digital micelles could be identified, sequence-decoded and quantified by MALDI and MALDI imaging at cellular, organ and tissue slice levels upon in vivo administration, enabling direct comparison of biological properties for each type of digital micelle in the same animal. The concept of digital micelles and encoded amphiphiles capable of direct sequencing and high-throughput label-free quantification could be exploited for next-generation precision nanomedicine designs (such as digital lipids) and protein corona studies.

DOI: 10.1038/s41557-022-01076-y

Source: https://www.nature.com/articles/s41557-022-01076-y