Digital micelles of encoded polymeric amphiphiles for direct sequence reading and ex vivo label-free quantification.
Qiangqiang ShiHao YinRundi SongJie XuJiajia TanXin ZhouJie CenZhengyu DengHuimin TongChenhui CuiYanfeng ZhangXiaopeng LiZhengbiao ZhangShiyong LiuPublished in: Nature chemistry (2022)
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.
Keyphrases
- label free
- drug delivery
- cancer therapy
- mass spectrometry
- drug release
- tandem mass spectrometry
- high resolution
- high throughput
- amino acid
- liquid chromatography
- high performance liquid chromatography
- ultra high performance liquid chromatography
- quantum dots
- working memory
- systematic review
- gas chromatography
- single cell
- small molecule
- ms ms
- solid phase extraction
- water soluble