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Designing dendrimers for biological applications

Abstract

Dendrimers are branched, synthetic polymers with layered architectures that show promise in several biomedical applications. By regulating dendrimer synthesis, it is possible to precisely manipulate both their molecular weight and chemical composition, thereby allowing predictable tuning of their biocompatibility and pharmacokinetics. Advances in our understanding of the role of molecular weight and architecture on the in vivo behavior of dendrimers, together with recent progress in the design of biodegradable chemistries, has enabled the application of these branched polymers as anti-viral drugs, tissue repair scaffolds, targeted carriers of chemotherapeutics and optical oxygen sensors. Before such products can reach the market, however, the field must not only address the cost of manufacture and quality control of pharmaceutical-grade materials, but also assess the long-term human and environmental health consequences of dendrimer exposure in vivo.

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Figure 1: Anatomy of a dendrimer.
Figure 2: Synthesis of a polyester dendron.
Figure 3: The variety of dendrimers used in biology.
Figure 4: Self-immolative dendrimers.
Figure 5: A simplified mathematical model predicting drug concentration in a tumor.
Figure 6: The effect of polymer architecture on glomerular filtration.
Figure 7: Dendritic polymer architectures.

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Acknowledgements

We are grateful for financial support of dendrimer drug carrier research from the National Institutes of Health (GM 65361 and EB 002047).

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Correspondence to Francis C Szoka.

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F.C.S. is an inventor on US patent no. 2,661,025, “Self-assembling polynucleotide delivery systems comprising dendrimer polycations.” The University of California has licensed this patent to Qiagen, from which the University of California and F.C.S. receive royalty income.

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Lee, C., MacKay, J., Fréchet, J. et al. Designing dendrimers for biological applications. Nat Biotechnol 23, 1517–1526 (2005). https://doi.org/10.1038/nbt1171

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