Chinese scholars have made progress in precision synthesis of polymer single-stranded bond selection chemistry and mass spectrometry sequencing

Figure 1 Direct reading of sequences that precisely encode amphiphilic polymers

Figure 2 Precisely encoded amphiphilic polymers with different sequences of self-assembly of digital micelles with controllable growth

Figure 3 Identification and label-free quantification of digital micelles at the organ and tissue section level

With the support of the National Natural Science Foundation of China (grant numbers: 51690150, 51690154, 52021002, 52233009 and U19A2094), Professor Liu Shiyong's research group, School of Chemistry and Materials Science, University of Science and Technology of China and Key Laboratory of Soft Matter Chemistry, Chinese Academy of Sciences, has made progress in the controllable synthesis of precision polymers and their functional applications micelles of encoded polymeric amphiphiles for direct sequence reading and ex vivo label-free quantification)", published online in the journal
Nature Chemistry on November 3, 2022 。 Link to the paper: _istranslated="1">.

Quantitatively studying the biodistribution of polymer nanoparticles is essential
to assess the efficacy and fate of nanomedicines.
Common fluorescence and isotope labeling techniques mainly rely on chemical modifications, which may change the physicochemical properties of polymer nanoparticles and affect their biodistribution
.
At the same time, traditional polymers are extremely challenging to quantify label-free polymers due to inherent characteristics such as wide molecular weight distribution, uneven chain length, and unclear sequence, and these inherent limitations also directly affect the clinical transformation
of polymer nanomedicines.

In response to the above challenges, the researchers first designed and created a series of precision-coded amphiphilic polymers consisting of photosensitive trigger motifs
, N-aryl carbamate repeating units and dendritic PEG (PEG dendron) with a modular synthesis strategy.
The synergistic effect of PEG dendron with supramolecular recognition of alkali metal ions (e.
g.
, sodium ions) and selective cleavage of benzyl-oxygen bonds in the backbone enables direct reading of the polymer sequence (Figure 1).

These novel precision-coded amphiphilic polymers can self-assemble into digital micelles of different morphologies that are tightly controlled by the polymer backbone sequence (Figure 2).

In addition, due to PEG dendron's enhanced sensitivity for the detection of precision-encoded amphiphilic polymer MALDI, the researchers further performed MALDI imaging of tissue sections, such as spleen sections, and revealed the spatial distribution of digital micelles in the organ (Figure 3).

This work provides a new idea for solving the problem of biodistribution quantification of polymer nanoparticles, and PEG dendron's enhanced MALDI quantification and decoding strategy can be further used for the sequencing and quantification of peptides/proteins/DNA and other natural/synthetic molecules
.