Biological applications of dendrimers

Cloninger, Mary J.

doi:10.1016/s1367-5931(02)00400-3

Cited by 501 publications

(313 citation statements)

References 56 publications

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“…Dendrimers-Dendrimers are often used as multivalent ligand scaffolds. [96,[136][137][138][139][140][141] An advantage of these ligands is that they can be fairly homogeneous; [96] this quality can aid in relating ligand features to biological activity. With beads or carrier protein conjugates, the sites of RE conjugation often are unknown; therefore, the population of conjugates is heterogeneous.…”

Section: 3dmentioning

confidence: 99%

Synthetic Multivalent Ligands as Probes of Signal Transduction

2006

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Cell surface receptors acquire information from the extracellular environment and coordinate intracellular responses. Evidence from biochemical and structural studies indicates that many receptors do not operate as individual entities, but rather as part of higher-order complexes (e.g. dimers and oligomers). Coupling the functions of multiple receptors may endow signaling pathways with the sensitivity and malleability required to govern cellular responses. Moreover, multireceptor signaling complexes may provide a means of spatially segregating otherwise degenerate signaling cascades. Despite the proposed importance of receptor-receptor processes in cellular signaling, questions concerning the mechanisms, extent, and consequences of receptor co-localization and interreceptor communication remain unanswered.Chemical synthesis can provide a variety of compounds with which to address the role of receptor assembly in signal transduction. The focus of this review is one such approach -the use of synthetic multivalent ligands to characterize receptor function. Multivalent ligands can be generated that possess a variety of sizes, shapes, valencies, orientations, and densities of binding elements. Their unique architectures imbue multivalent ligands with the ability to access binding modes not available to monovalent compounds. Multivalent ligands, therefore, are capable of illuminating aspects of inter-receptor processes that are not readily probed using conventional approaches. We suggest that, as focus shifts from investigations of the function of individual proteins and toward the analysis of multi-receptor signaling complexes, multivalent ligands will become even more valuable tools with which to ask sophisticated mechanistic questions. Further, multivalent ligands may provide new opportunities for manipulating receptor systems for the deconvolution of pathways, diagnosis, and, ultimately, the treatment of disease.

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Section: 3dmentioning

confidence: 99%

Synthetic Multivalent Ligands as Probes of Signal Transduction

2006

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“…Novel strategies have been implemented to build up well defined constructs featuring selfassembling capabilities in the presence of nucleic acids. In this context, the unique characteristics of dendrimers and other highly ordered clusters, such as uniformity, monodispersity and multivalency, have attracted increasing attention (5)(6)(7)(8). Homogeneous external functionalization of these platforms becomes, however, exponentially more complicated as the dendrimer generation increases (9)(10).…”

Section: Introductionmentioning

confidence: 99%

Insights in cellular uptake mechanisms of pDNA–polycationic amphiphilic cyclodextrin nanoparticles (CDplexes)

Díaz‐Moscoso

Vercauteren

Rejman

et al. 2010

Journal of Controlled Release

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have equally contributed to the reported work. Abstr actIt is generally recognized that the major obstacle to efficient gene delivery is cellular internalization and endosomal escape of the DNA. Recently, we have developed a modular strategy for the preparation of well-defined polycationic amphiphilic cyclodextrins (paCDs) capable of complexing and compacting DNA into homogeneous nanoparticles (<70 nm).Since paCDs resemble both cationic polymers and cationic lipids, it is conceivable that the corresponding pDNA-paCD nanoparticles (CDplexes) might use the cell uptake and endosomal escape mechanisms described for both lipoplexes and polyplexes. To verify this hypothesis, we have now investigated the uptake and transfection efficiencies of CDplexes in the presence of several inhibitors of endocytosis, namely chlorpromazine, genistein, dynasore and methylated β-cyclodextrin (MbCD). Our data show that CDplexes obtained from paCD 1, which ranks among the most efficient paCD gene vectors reported up to date, are internalized by both clathrin-dependent (CDE) and clathrin-independent endocytosis (CIE), both processes being cholesterol-and dynamin-dependent. We observed that the largest fraction of gene complexes is taken up via CDE, but this fraction is less relevant for transfection. The smaller fraction that is internalized via the CIE pathway is predominantly responsible for successful transfection. Intr oductionThe successful delivery of therapeutic genes into cells and their availability at the intracellular site of action are crucial requirements for successful gene therapy. During the last decade, under the advent of nanotechnology, a broad diversity of creative materials featuring promising properties for nonviral gene delivery applications has emerged, (1). Cationic polymers and lipids, or their combinations, have shown the ability to bind nucleic acids through electrostatic interactions and condense them into complexes that can be readily internalized by cells (2-3). The gene delivering capabilities of many of these systems have been thoroughly investigated. Yet, drawing firm conclusions that might serve to provide feedback for the design of improved delivery entities is a delicate issue as a consequence of the essentially polydisperse nature of such structures (4).The control of the architecture of multifunctional macromolecules is a major determinant in the rational design of successful nonviral gene delivery systems. Novel 3 strategies have been implemented to build up well defined constructs featuring selfassembling capabilities in the presence of nucleic acids. In this context, the unique characteristics of dendrimers and other highly ordered clusters, such as uniformity, monodispersity and multivalency, have attracted increasing attention (5-8). Homogeneous external functionalization of these platforms becomes, however, exponentially more complicated as the dendrimer generation increases (9-10). The use of preorganized macrocyclic scaffolds, such as calixarenes, to achieve a precise alignment of functiona...

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“…The unique architecture and monodispersity of dendrimers allow their principle use as molecular cages for a direct transport of different guest molecules like drugs and DNA [1][2][3][4]. Complexes of dendrimers with these compounds in water solutions at neutral or low pH are stabilized mainly due to the electrostatic forces.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of Complexation of a Charged Dendrimer by Linear Polyelectrolyte: Computer Modelling

Lyulin

Darinskii

2007

E-Polymers

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Brownian-dynamics simulations have been performed for complexes formed by a charged dendrimer and a long oppositely charged linear polyelectrolyte when overcharging phenomenon is always observed. After complex formation the orientational mobility of the individual dendrimer bonds, the fluctuations of the dendrimer size, and the dendrimer rotational diffusion have been simulated. Corresponding relaxation times do not depend on the linear-chain length in a complex and are close to those for a single neutral dendrimer. At the same time fluctuations of the size of a complex are completely defined by the corresponding fluctuations of a linear polyelectrolyte size. Adsorbed polyelectrolyte practically does not feel the rotation of a dendrimer; simulated complexes may be considered as nuts with light core (dendrimer) and heavy shell (adsorbed linear polymer); the electrostatic contacts between dendrimer and oppositely charged linear polymer are easily broken due to the very fast dendrimer-size fluctuations.

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Biological applications of dendrimers

Cited by 501 publications

References 56 publications

Synthetic Multivalent Ligands as Probes of Signal Transduction

Synthetic Multivalent Ligands as Probes of Signal Transduction

Insights in cellular uptake mechanisms of pDNA–polycationic amphiphilic cyclodextrin nanoparticles (CDplexes)

Dynamics of Complexation of a Charged Dendrimer by Linear Polyelectrolyte: Computer Modelling

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