Dendritic oligoguanidines as intracellular translocators

Chung, Hyun-Ho; Harms, Guido; Seong, Churl Min; Choi, Byung Hyune; Min, Changwook; Taulane, Joseph P.; Goodman, Murray

doi:10.1002/bip.10597

Cited by 54 publications

(57 citation statements)

References 14 publications

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“…Goodman and coworkers reported a series of polyguanidinylated dendritic structures that readily enter cells (11-15, Fig. 3) [26]. The dendritic oligoguanidines were conjugated to fluorescein and to a mutant green fluorescent protein (GFP).…”

Section: Dendrimeric and Branched Grtsmentioning

confidence: 99%

The design of guanidinium-rich transporters and their internalization mechanisms

Wender

Galliher

Goun

et al. 2008

Advanced Drug Delivery Reviews

376

337

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The ability of a drug or probe to cross a biological barrier has historically been viewed to be a function of its intrinsic physical properties. This view has largely restricted drug design and selection to agents within a narrow log P range. Molecular transporters offer a strategy to circumvent these restrictions. In the case of guanidinium-rich transporters (GRTs), a typically highly water-soluble conjugate is found to readily pass through the non-polar membrane of a cell and for some across tissue barriers. This activity opens a field of opportunities for the use of GRTs to enable delivery of polar and nonpolar drugs or probes as well as to enhance uptake of those of intermediate polarity. The field of transporter enabled or enhanced uptake has grown dramatically in the last decade. Some GRT drug conjugates have been advanced into clinical trials. This review will provide an overview of recent work pertinent to the design and mechanism of uptake of GRTs.

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Section: Dendrimeric and Branched Grtsmentioning

confidence: 99%

The design of guanidinium-rich transporters and their internalization mechanisms

Wender

Galliher

Goun

et al. 2008

Advanced Drug Delivery Reviews

376

337

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“…In fact, guanidinium-containing peptoids (9) and ␤-peptides exhibit useful cell uptake properties (10). Short polyproline-based helices appended with guanidinium groups (11), highly branched guanidinium-rich dendritic oligomers (12), and heterocyclic guanidinium vectors also serve as cell transporters (13).…”

mentioning

confidence: 99%

Guanidinylated Neomycin Delivers Large, Bioactive Cargo into Cells through a Heparan Sulfate-dependent Pathway

Elson-Schwab

Garner

Schuksz

et al. 2007

Journal of Biological Chemistry

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Facilitating the uptake of molecules into living cells is of substantial interest for basic research and drug delivery applications. Arginine-rich peptides have been shown to facilitate uptake of high molecular mass cargos into cells, but the mechanism of uptake is complex and may involve multiple receptors. In this report, we show that a derivative of the aminoglycoside antibiotic neomycin, in which all of the ammonium groups have been converted into guanidinium groups, can carry large (>300 kDa) bioactive molecules across cell membranes. Delivery occurs at nanomolar transporter concentrations and under these conditions depends entirely on cell surface heparan sulfate proteoglycans. Conjugation of guanidinoneomycin to the plant toxin saporin, a ribosome-inactivating agent, results in proteoglycan-dependent cell toxicity. In contrast, an arginine-rich peptide shows both heparan sulfate-dependent and -independent cellular uptake. The high selectivity of guanidinoneomycin for heparan sulfate suggests the possibility of exploiting differences in proteoglycan compositions to target delivery to different cell types.

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“…It had been previously demonstrated by the groups of Goodman, (Chung et al, 2004) Wender (Wender et al, 2005), and Harth (Huang et al, 2007) that it was possible to prepare dendrons functionalized at their peripheries with guanidines and that these could enhance the uptake of chromophores into cells in a manner similar to HIV-Tat and protamine, which contain high levels of the amino acid arginine. Thus, the concept of dendritic cell-penetrating agents seemed promising, but these agents had not previously been demonstrated to deliver large payloads such as nanoparticles into cells.…”

Section: Dendritic Functionalization Of Spiomentioning

confidence: 99%

Dendritic surface functionalization of nanomaterials: controlling properties and functions for biomedical applications

Nazemi

Gillies

2013

Braz. J. Pharm. Sci.

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A wide variety of nanomaterials have demonstrated promise in medical applications such as drug delivery and imaging. In these applications, the surface chemistry of the materials is critical as it plays an important role in determining the toxicity and biodistribution behavior of the material. We review here the functionalization of nanomaterials with dendrons as an efficient method to alter the surface chemistry of the materials, introducing new properties and functions. Described here is the functionalization of superparamagnetic iron oxide nanoparticles (SPIO) with dendritic guanidines to enhance their transport into cells for magnetic resonance imaging applications. The introduction of dendrons bearing peripheral hydroxyls, amines, guanidines, carbohydrates and Gd(III) chelates to polymer vesicles (polymersomes) is also described. These dendritic moieties allow for modulation of toxicity, cell uptake, protein binding, and contrast agent efficiency, while at the same time allowing the stabilities of the polymersomes to be maintained. Thus, this approach holds promise for the development of a wide range of multifunctional materials for pharmaceutical applications.

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Dendritic oligoguanidines as intracellular translocators

Cited by 54 publications

References 14 publications

The design of guanidinium-rich transporters and their internalization mechanisms

The design of guanidinium-rich transporters and their internalization mechanisms

Guanidinylated Neomycin Delivers Large, Bioactive Cargo into Cells through a Heparan Sulfate-dependent Pathway

Dendritic surface functionalization of nanomaterials: controlling properties and functions for biomedical applications

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