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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.
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Probes for noninvasive biological visualization and biosensing of cancer cells
The early detection of tumors and precancerous conditions is vital for cancer diagnosis. Advances in fluorescence microscopic techniques and materials synthesis processes have revolutionized biomarker detection and image-guided cancer surveillance. In particular, novel materials-based diagnostic tools and innovative therapies have facilitated a precise understanding of biological processes at the molecular level. This critical review presents an overview of bioimaging probes, including functionalized chromophoric systems, non-functionalized chromophoric systems, and nanoscale biosensors. Technical challenges and future directions related to these approaches are considered.
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- Award ID(s):
- 2029974
- PAR ID:
- 10502548
- Publisher / Repository:
- AIP Publishing
- Date Published:
- Journal Name:
- Applied Physics Reviews
- Volume:
- 10
- Issue:
- 4
- ISSN:
- 1931-9401
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1063/5.0166740
