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

• Published in: Nature chemistry 2023-02, Vol.15 (2), p.257-270
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 631/1647/296; 631/61/54/989; 639/638/298/923/966; 639/638/455/941; 639/925/357/341; Alkali metals; Analytical Chemistry; Animals; Biochemistry; Biological properties; Biomedical materials; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Inorganic Chemistry; Ionization; Ions; Lipids; Mass spectrometry; Mass spectroscopy; Metal ions; Micelles; Modular construction; Nanoparticles; Nanotechnology; Nucleotide sequence; Organic Chemistry; Physical Chemistry; Polyethylene glycol; Polyethylene Glycols - chemistry; Polymers; Polymers - chemistry; Scaffolding; Self-assembly; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods
• ISSN: 1755-4330; 1755-4349
• DOI: 10.1038/s41557-022-01076-y

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. Identifying and quantifying the biodistribution of synthetic polymeric nanoparticles in biological milieu is crucial for biomedical applications. Now, it has been shown that encoded polymeric amphiphiles with discrete molar masses undergo sequence- and length-dependent self-assembly into precise digital micelles that can be used in direct sequence reading and ex vivo label-free quantification assays.