Cytosolic Delivery of Single-Chain Polymer Nanoparticles

Naomi M. Hamelmann, Jan Willem D. Paats, Jos M.J. Paulusse*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)
84 Downloads (Pure)


Cytosolic delivery of therapeutic agents is key to improving their efficacy, as the therapeutics are primarily active in specific organelles. Single-chain polymer nanoparticles (SCNPs) are a promising nanocarrier platform in biomedical applications due to their unique size range of 5-20 nm, modularity, and ease of functionalization. However, cytosolic delivery of SCNPs remains challenging. Here, we report the synthesis of active ester-functional SCNPs of approximately 10 nm via intramolecular thiol-Michael addition cross-linking and their functionalization with increasing amounts of tertiary amines 0 to 60 mol % to obtain SCNPs with increasing positive surface charges. No significant cytotoxicity was detected in bEND.3 cells for the SCNPs, except when SCNPs with high amounts of tertiary amines were incubated over prolonged periods of time at high concentrations. Cellular uptake of the SCNPs was analyzed, presenting different uptake behavior depending on the degree of functionalization. Confocal microscopy revealed successful cytosolic delivery of SCNPs with high degrees of functionalization (45%, 60%), while SCNPs with low amounts (0% to 30%) of tertiary amines showed high degrees of colocalization with lysosomes. This work presents a strategy to direct the intracellular location of SCNPs by controlled surface modification to improve intracellular targeting for biomedical applications.

Original languageEnglish
Pages (from-to)1443-1449
Number of pages7
JournalACS macro letters
Issue number11
Publication statusPublished - 5 Nov 2021


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