The effect of charge and albumin on cellular uptake of supramolecular polymer nanostructures

Jiankang Song, Peter Paul K.H. Fransen, Maarten H. Bakker, Sjors P.W. Wijnands, Jingyi Huang, Shuaiqi Guo, Patricia Y.W. Dankers (Corresponding author)

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Intracellular delivery of functional biomolecules by using supramolecular polymer nanostructures has gained significant interest. Here, various charged supramolecular ureido-pyrimidinone (UPy)-aggregates were designed and formulated via a simple “mix-and-match” method. The cellular internalization of these UPy-aggregates in the presence or absence of serum proteins by phagocytic and non-phagocytic cells, i.e., THP-1 derived macrophages and immortalized human kidney cells (HK-2 cells), was systematically investigated. In the presence of serum proteins the UPy-aggregates were taken up by both types of cells irrespective of the charge properties of the UPy-aggregates, and the UPy-aggregates co-localized with mitochondria of the cells. In the absence of serum proteins only cationic UPy-aggregates could be effectively internalized by THP-1 derived macrophages, and the internalized UPy-aggregates either co-localized with mitochondria or displayed as vesicular structures. While the cationic UPy-aggregates were hardly internalized by HK-2 cells and could only bind to the membrane of HK-2 cells. With adding and increasing the amount of serum albumin in the cell culture medium, the cationic UPy-aggregates were gradually taken up by HK-2 cells without anchoring on the cell membranes. It is proposed that the serum albumin regulates the cellular internalization of UPy-aggregates. These results provide fundamental insights for the fabrication of supramolecular polymer nanostructures for intracellular delivery of therapeutics.

Originele taal-2Engels
Pagina's (van-tot)4854-4866
Aantal pagina's13
TijdschriftJournal of Materials Chemistry B
Nummer van het tijdschrift20
Vroegere onlinedatum9 apr. 2024
StatusGepubliceerd - 22 mei 2024


Seventh Framework Programme
Dutch Federation of University Medical Centers
Royal Netherlands Academy of Sciences
Hartstichting, Nederlandse
Netherlands Cardiovascular Research InitiativeCVON 2012-01
European Research Council308045
European Research Council
Ministerie van OCW024.005.020, 024.003.013
Ministerie van OCW


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