This is the challenge that Tanushree Gupta Gupta of Andrey Klymchenko’s team took on in a recent study: using polysarcosine (PSar), a peptide, to design stealth polymeric nanoparticles with an optimized chain length. Their results, recently published in Aggregate, pave the way for a new generation of safer and more effective nanomaterials.
The team functionalized nanoparticles encapsulating a fluorescent dye (rhodamine) with PSar chains of varying lengths (5 to 19 units). The results are promising:
• Increased colloidal stability in physiological media, even for initially unstable NPs.
• Reduced nonspecific interactions: the longer the PSar chain, the less the NPs interact with blood serum proteins or living cells.
• Charge neutrality: NPs grafted with 19-mer PSar achieve a surface charge close to neutrality, limiting their aggregation and detection by the immune system.
Result: Nanoparticles functionalized with 19-mer PSar exhibit minimal interactions with cells and surfaces, while enabling specific targeting (via the HaloTag ligand) for cellular imaging.
PSar offers an alternative to PEG by providing greater chemical stability and lower immunogenicity, while allowing for synthesis with controlled chain lengths. Furthermore, a short chain of only 19 units is sufficient to achieve stealth properties, which simplifies manufacturing and reduces costs. Finally, this approach could be adapted to other nanomaterials, thereby improving their safety and efficacy in complex biological environments.
This work suggests that short-chain PSar could become a standard for the design of stealth nanoparticles, with promising applications in bioimaging for precise cell tracking, in biodetection for targeted diagnostics, and in targeted therapies for drug delivery.
Congratulations to the authors!
