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WIREs Nanomed Nanobiotechnol

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Dendrimer‐based nanocarriers: a versatile platform for drug delivery

Advanced Review

Hao‐Jui Hsu, Jason Bugno, Seung‐ri Lee, Seungpyo Hong

Published Online: Apr 29 2016

DOI: 10.1002/wnan.1409

Full article on Wiley Online Library: HTML PDF

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Advances in nanotechnology have had profound impacts on therapeutic delivery, leading to the development of nanomaterials engineered with large carrying capabilities and targeting functionalities. Among the nanomaterials, dendrimers have garnered particular attention from researchers owing to their well‐defined structure, near‐monodispersity, and ease of multifunctionalization. As hyperbranched, three‐dimensional macromolecules, dendrimers can be engineered to target and deliver a wide range of therapeutic agents, including small molecules, peptides, and genes, reducing their systemic toxicities and enhancing efficacies. In this review, we provide a comprehensive overview of the commonly employed dendrimer‐based nanocarrier designs, including dendrimer conjugates, Janus dendrimers, and linear‐dendritic block copolymers. The discussion will progress through the basic synthetic strategies of dendrimer‐based nanocarriers, followed by the potential clinical applications related to their unique structural properties. Finally, the major challenges that these nanocarriers are currently facing in their clinical translation and possible solutions to address these issues will be discussed, with the aim to provide researchers in the drug delivery field a good understanding of the potential utilities of dendrimer‐based nanocarriers. WIREs Nanomed Nanobiotechnol 2017, 9:e1409. doi: 10.1002/wnan.1409 This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Representative synthetic routes for dendrimers: (a) convergent and (b) divergent approaches.

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Prevention of viral infection using surface‐modified dendrimers through (a) direct binding to the viral epitope or (b) prebinding to receptors of host cells.

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An illustration of a hybrid nanoparticle (NP) system that combines targeted dendrimers and PEGylated polymeric NPs to achieve sequential passive and ligand‐mediated targeting. The PEGylated, larger NP shell allows the hybrid NPs to passively accumulate at the tumor site through the enhanced permeability and retention (EPR) effect. The folic acid (FA)‐targeted dendrimers can be released from the carrier NPs and permeate the tumor mass to actively bind to tumor cells. (Reprinted with permission from Ref . Copyright 2014 Elsevier)

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A linear‐dendritic block copolymer (LDBC)‐based micelle system that exhibits superior hydrodynamic stability to linear‐block copolymer‐based micelles. (a) An illustration of a self‐assembled LDBC micelle built from polycaprolactone (PCL)‐polyester G3‐poly(ethylene glycol) (PEG) copolymers. (b) Critical micelle concentration (CMC) comparison of LDBCs (red circle) and linear‐block copolymers (blue square). LDBCs exhibit lower CMCs than linear‐block copolymers in the same hydrophilic–lipophilic balance (HLB) range, demonstrating the improved thermodynamic stability of the LDBC‐based micelles. (Reprinted with permission from Ref . Copyright 2011 Royal Society of Chemistry)

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Linear‐dendritic block copolymer (LDBC) synthetic strategies: (a) coupling, (b) linear polymer‐first, and (c) dendron‐first.

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Synthetic strategies of Janus dendrimers: (a) direct focal conjugation of two dendrons with complementary focal groups, (b) conjugation of two dendrons via a multifunctional linker, and (c) growth of the second dendron from the focal point of the first dendron.

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Commonly used dendrimers in drug delivery: (a) a schematic illustration showing the three components of a dendrimer molecule and chemical structures of (b) poly(amidoamine) (PAMAM), (c) poly(propylenimine) (PPI), and (d) poly(l‐lysine) (PLL) dendrimers.

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Further Reading

Blanco, E, Shen, H, Ferrari, M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol 2015, 33:941–951.
Couvreur, P. Nanoparticles in drug delivery: past, present and future. Adv Drug Deliv Rev 2013, 65:21–23.
Prabhakar, U, Maeda, H, Jain, RK, Sevick‐Muraca, EM, Zamboni, W, Farokhzad, OC, Barry, ST, Gabizon, A, Grodzinski, P, Blakey, DC. Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology. Cancer Res 2013, 73:2412–2417.

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