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.

Designing dendrimers for biological applications.

Laboratoire de Génie Enzymatique et Biomoléculaire, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, 43 Boulevard du 11 Novembre 1918, Villeurbanne F-69622, France, UMR5246, Centre National de La Recherche Scientifque, Villeurbanne F-69622, France, Université de Lyon, Lyon F-69622, France, Université Lyon 1, Lyon F-69622, France, Institut National des Sciences Appliquées de Lyon, EÄ cole d’Ingénieurs, Villeurbanne F-69621, France, and EÄ cole Supérieure Chimie Physique EÄ lectronique de Lyon, Villeurbanne F-69616, France

DNA biosensors and microarrays.

Dendrimers are characterized by a combination of high end-group functionality and a compact, precisely defined molecular structure. These characteristics can be used in biomedical applications, for example, for the amplification or multiplication of effects on a molecular level, or to create extremely high local concentrations of drugs, molecular labels, or probe moieties. A brief summary of the current state of the art in the field is given, and focuses on the application of dendrimers both in diagnostics as well as in therapy. In diagnostics, dendrimers that bear GdIII complexes are used as contrast agents in magnetic resonance imaging. DNA dendrimers have potential for routine use in high-throughput functional genomic analysis, as well as for DNA biosensors. Dendrimers are also being investigated for therapeutics, for example, as carriers for controlled drug delivery, in gene transfection, as well as in boron neutron-capture therapy. Furthermore, the antimicrobial activity of dendrimers has been studied.

Dendritic polymers in biomedical applications: from potential to clinical use in diagnostics and therapy.

The combination of nanostructures with biomolecules leading to the generation of functional nanosystems holds great promise for biotechnological and biomedical applications. As a naturally occurring biomacromolecule, DNA exhibits excellent biocompatibility and programmability. Also, scalable synthesis can be readily realized through automated instruments. Such unique properties, together with Watson–Crick base-pairing interactions, make DNA a particularly promising candidate to be used as a building block material for a wide variety of nanostructures. In the past few decades, various DNA nanostructures have been developed, including one-, two- and three-dimensional nanomaterials. Aptamers are single-stranded DNA or RNA molecules selected by Systematic Evolution of Ligands by Exponential Enrichment (SELEX), with specific recognition abilities to their targets. Therefore, integrating aptamers into DNA nanostructures results in powerful tools for biosensing and bioimaging applications. Furthermore, owing to their high loading capability, aptamer-modified DNA nanostructures have also been altered to play the role of drug nanocarriers for in vivo applications and targeted cancer therapy. In this review, we summarize recent progress in the design of aptamers and related DNA molecule-integrated DNA nanostructures as well as their applications in biosensing, bioimaging and cancer therapy. To begin with, we first introduce the SELEX technology. Subsequently, the methodologies for the preparation of aptamer-integrated DNA nanostructures are presented. Then, we highlight their applications in biosensing and bioimaging for various targets, as well as targeted cancer therapy applications. Finally, we discuss several challenges and further opportunities in this emerging field.

Aptamer-integrated DNA nanostructures for biosensing, bioimaging and cancer therapy

Rapid, multiplexed, sensitive and specific molecular detection is of great demand in gene profiling, drug screening, clinical diagnostics and environmental analysis. One of the major challenges in multiplexed analysis is to identify each specific reaction with a distinct label or 'code'. Two encoding strategies are currently used: positional encoding, in which every potential reaction is preassigned a particular position on a solid-phase support such as a DNA microarray, and reaction encoding, where every possible reaction is uniquely tagged with a code that is most often optical or particle based. The micrometer size, polydispersity, complex fabrication process and nonbiocompatibility of current codes limit their usability. Here we demonstrate the synthesis of dendrimer-like DNA-based, fluorescence-intensity-coded nanobarcodes, which contain a built-in code and a probe for molecular recognition. Their application to multiplexed detection of the DNA of several pathogens is first shown using fluorescence microscopy and dot blotting, and further demonstrated using flow cytometry that resulted in detection that was sensitive (attomole) and rapid.

/pdf/multiplexed-detection-of-pathogen-dna-with-dna-based-40ksa39zw8.pdf

Multiplexed detection of pathogen DNA with DNA-based fluorescence nanobarcodes

Dendritic Nucleic Acid Structures

A novel class of reagents for assaying nucleic acid sequences comprise successive layers of polynucleotides of a specific structure, including a double-stranded waist and single-stranded, free arms at the molecule ends, formed by hybridization of the arms to adjacent molecule arms. The reagent is used to assay for specific nucleic acid sequences. The outer layer of polynucleotides are specific for the sequence to be assayed through their non-annealed, free, single-stranded arms. The reagents are useful in the assay of a wide variety of nucleic acid sequences including those associated with pathogens such as pathogenic bacteria and virus.

Reagents for detecting and assaying nucleic acid sequences

A novel class of reagents for assaying nucleic acid sequences comprise successive layers of polynucleotides of a specific structure, including a double-stranded waist and single-stranded, free arms at the molecule ends, formed by hybridization of the arms to adjacent molecule arms. The reagent is used to assay for specific nucleic acid sequences. The outer layer of polynucleotides are specific for the sequence to be assayed through their non-annealed, free, single-stranded arms. The reagents are useful in the assay of a wide variety oil nucleic acid sequences including those associated with pathogens such as pathogenic bacteria and virus.

Nucleic acid matrices

Methods for detecting and assaying nucleic acid sequences

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Dendritic Nucleic Acid Structures

Reagents for detecting and assaying nucleic acid sequences

Nucleic acid matrices

Methods for detecting and assaying nucleic acid sequences