Issue 10, 2025

The toxicity, uptake, and impact on galectin-3 mediated apoptosis of lactose functionalized PAMAM dendrimers

Abstract

Poly(amidoamine) (PAMAM) dendrimers functionalized with ligands that are designed to interact with biological receptors are important macromolecules for the elucidation and mediation of biological recognition processes. Specifically, carbohydrate functionalized dendrimers are useful synthetic multivalent systems for the study of multivalent protein–carbohydrate interactions. For example, lactose functionalized glycodendrimers can be used to discern the function of galectins, galactoside-binding proteins that are often over-expressed during cancer progression. In order to effectively interpret cancer cellular assays using glycodendrimers, however, their properties in the presence of cells must first be assessed. Macromolecules that are taken up by cells would be expected to have access to many different cell signaling pathways and modes of action that solely extracellular macromolecules cannot utilize. In addition, macromolecules that display cellular toxicity could not be used as drug delivery vehicles. Here, we report fundamental studies of cellular toxicity, viability, and uptake with four generations of lactose functionalized PAMAM dendrimers. In all cases, the dendrimers are readily taken up by the cells but do not display any significant cellular toxicity. The glycodendrimers also increase cellular apoptosis, suggesting that they may abrogate the antiapoptotic protections afforded by galectin-3 to cancer cells. The results reported here indicate that appropriately functionalized PAMAM dendrimers can be used as nontoxic tools for the study and mediation of both extra and intracellular cancer processes.

Graphical abstract: The toxicity, uptake, and impact on galectin-3 mediated apoptosis of lactose functionalized PAMAM dendrimers

Supplementary files

Article information

Article type
Paper
Submitted
02 Aug 2024
Accepted
02 Apr 2025
First published
10 Apr 2025
This article is Open Access
Creative Commons BY license

Mater. Adv., 2025,6, 3171-3184

The toxicity, uptake, and impact on galectin-3 mediated apoptosis of lactose functionalized PAMAM dendrimers

M. S. Fricke, M. R. Frometa, Y. Kerkhoff, S. P. Bernhard, R. S. Tahir, E. Quaas, W. H. Totten, R. Haag, K. Achazi and M. J. Cloninger, Mater. Adv., 2025, 6, 3171 DOI: 10.1039/D4MA00782D

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