RESUMO
Lipid DNA nanoparticles (NPs) exhibit an intrinsic affinity to the ocular surface and can be loaded by hybridization with fluorophore-DNA conjugates or with the anti-glaucoma drug travoprost by hybridizing an aptamer that binds the medication. In the travoprost-loaded NPs (Trav-NPs), the drug is bound by specific, non-covalent interactions, not requiring any chemical modification of the active pharmaceutical ingredient. Fluorescently labeled Trav-NPs show a long-lasting adherence to the eye, up to sixty minutes after eye drop instillation. Biosafety of the Trav-NPs was proved and in vivo. Ex vivo and in vivo quantification of travoprost via LC-MS revealed that Trav-NPs deliver at least twice the amount of the drug at every time-point investigated compared to the pristine drug. The data successfully show the applicability of a DNA-based drug delivery system in the field of ophthalmology for the treatment of a major retinal eye disease, i.e. glaucoma.
Assuntos
DNA/química , Sistemas de Liberação de Medicamentos , Glaucoma/tratamento farmacológico , Nanopartículas/química , Animais , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/farmacologia , Contenção de Riscos Biológicos , DNA/farmacologia , Modelos Animais de Doenças , Humanos , Lipídeos/química , Lipídeos/farmacologia , Camundongos , Ratos , Suínos , Travoprost/química , Travoprost/farmacologiaRESUMO
Reversible control over the functionality of biological systems via external triggers may be used in future medicine to reduce the need for invasive procedures. Additionally, externally regulated biomacromolecules are now considered as particularly attractive tools in nanoscience and the design of smart materials, due to their highly programmable nature and complex functionality. Incorporation of photoswitches into biomolecules, such as peptides, antibiotics, and nucleic acids, has generated exciting results in the past few years. Molecular motors offer the potential for new and more precise methods of photoregulation, due to their multistate switching cycle, unidirectionality of rotation, and helicity inversion during the rotational steps. Aided by computational studies, we designed and synthesized a photoswitchable DNA hairpin, in which a molecular motor serves as the bridgehead unit. After it was determined that motor function was not affected by the rigid arms of the linker, solid-phase synthesis was employed to incorporate the motor into an 8-base-pair self-complementary DNA strand. With the photoswitchable bridgehead in place, hairpin formation was unimpaired, while the motor part of this advanced biohybrid system retains excellent photochemical properties. Rotation of the motor generates large changes in structure, and as a consequence the duplex stability of the oligonucleotide could be regulated by UV light irradiation. Additionally, Molecular Dynamics computations were employed to rationalize the observed behavior of the motor-DNA hybrid. The results presented herein establish molecular motors as powerful multistate switches for application in biological environments.
Assuntos
Compostos Azo/química , DNA/síntese química , Simulação de Dinâmica Molecular , Teoria Quântica , DNA/química , Estrutura Molecular , Hibridização de Ácido Nucleico , Processos Fotoquímicos , Estereoisomerismo , Raios UltravioletaRESUMO
Hydrophobic drug candidates require innovative formulation agents. We designed and synthesized lipid-DNA polymers containing varying numbers of hydrophobic alkyl chains. The hydrophobicity of these amphiphiles is easily tunable by introducing a defined number of alkyl chain-modified nucleotides during standard solid-phase synthesis of DNA using an automated DNA synthesizer. We observed that the resulting self-assembled micelles solubilize the poorly water-soluble drug, meta-tetra-hydroxyphenyl-chlorin (mTHPC) used in photodynamic therapy (PDT) with high loading concentrations and loading capacities. A cell viability study showed that mTHPC-loaded micelles exhibit good biocompatibility without irradiation, and high PDT efficacy upon irradiation. Lipid-DNAs provide a novel class of drug-delivery vehicle, and hybridization of DNA offers a potentially facile route for further functionalization of the drug-delivery system with, for instance, targeting or imaging moieties.
RESUMO
Anchoring DNA via hydrophobic units into the membrane of vesicles allows tagging of these nanocontainers with sequence information. Moreover, the hybridization of DNA on the surface of liposomes enables sequence specific functionalization, vesicle aggregation, and vesicle fusion. Specifically, DNA-hybridization-based approaches for fusion employing oligonucleotides terminally modified with one or two anchoring units were hindered by a limited degree of full fusion or by significant leakage during fusion. The current work deals with a new strategy for anchoring oligonucleotides on a membrane by lipid-modified nucleobases rather than by attaching hydrophobic units to the 3'- or 5'-termini. The lipid anchors were incorporated into the DNA sequence via phosphoramidite nucleotide building blocks during automated solid-phase synthesis allowing variation of the number and position of hydrophobic units along the DNA backbone. Single-stranded DNA functionalized with four lipid-modified nucleobases was stably grafted onto the membrane of lipid vesicles. It was found that the orientation of DNA hybridization and the number of anchoring units play a crucial role in liposomal fusion, which in the most efficient system reached remarkable 29 % content mixing without notable leakage.
Assuntos
DNA de Cadeia Simples/química , Lipossomos/química , Microscopia Crioeletrônica , Difusão Dinâmica da Luz , Transferência Ressonante de Energia de Fluorescência , Interações Hidrofóbicas e Hidrofílicas , Hibridização de Ácido NucleicoRESUMO
Photosynthesis is Nature's major process for converting solar into chemical energy. One of the key players in this process is the multiprotein complex photosystem I (PSI) that through absorption of incident photons enables electron transfer, which makes this protein attractive for applications in bioinspired photoactive hybrid materials. However, the efficiency of PSI is still limited by its poor absorption in the green part of the solar spectrum. Inspired by the existence of natural phycobilisome light-harvesting antennae, we have widened the absorption spectrum of PSI by covalent attachment of synthetic dyes to the protein backbone. Steady-state and time-resolved photoluminescence reveal that energy transfer occurs from these dyes to PSI. It is shown by oxygen-consumption measurements that subsequent charge generation is substantially enhanced under broad and narrow band excitation. Ultimately, surface photovoltage (SPV) experiments prove the enhanced activity of dye-modified PSI even in the solid state.
Assuntos
Corantes Fluorescentes/química , Compostos Heterocíclicos de 4 ou mais Anéis/química , Complexo de Proteína do Fotossistema I/química , Cianobactérias/química , Transferência de Energia , Transferência Ressonante de Energia de Fluorescência , Concentração de Íons de Hidrogênio , Luminescência , Lisina/química , Microscopia Eletrônica de Transmissão , Oxigênio/química , Oxigênio/metabolismoRESUMO
Reversible noncovalent but sequence-dependent attachment of DNA to gels is shown to allow programmable mobility processing of DNA populations. The covalent attachment of DNA oligomers to polyacrylamide gels using acrydite-modified oligonucleotides has enabled sequence-specific mobility assays for DNA in gel electrophoresis: sequences binding to the immobilized DNA are delayed in their migration. Such a system has been used for example to construct complex DNA filters facilitating DNA computations. However, these gels are formed irreversibly and the choice of immobilized sequences is made once off during fabrication. In this work, we demonstrate the reversible self-assembly of gels combined with amphiphilic DNA molecules, which exhibit hydrophobic hydrocarbon chains attached to the nucleobase. This amphiphilic DNA, which we term lipid-DNA, is synthesized in advance and is blended into a block copolymer gel to induce sequence-dependent DNA retention during electrophoresis. Furthermore, we demonstrate and characterize the programmable mobility shift of matching DNA in such reversible gels both in thin films and microchannels using microelectrode arrays. Such sequence selective separation may be employed to select nucleic acid sequences of similar length from a mixture via local electronics, a basic functionality that can be employed in novel electronic chemical cell designs and other DNA information-processing systems.
Assuntos
DNA/química , Eletroforese Capilar/métodos , Lipídeos/química , Técnicas Analíticas Microfluídicas/métodos , Sequência de Bases , MicroeletrodosRESUMO
DNA-incorporating hydrophobic moieties can be synthesized by either solid-phase or solution-phase coupling. On a solid support the DNA is protected, and hydrophobic units are usually attached employing phosphoramidite chemistry involving a DNA synthesizer. On the other hand, solution coupling in aqueous medium results in low yields due to the solvent incompatibility of DNA and hydrophobic compounds. Hence, the development of a general coupling method for producing amphiphilic DNA conjugates with high yield in solution remains a major challenge. Here, we report an organic-phase coupling strategy for nucleic acid modification and polymerization by introducing a hydrophobic DNA-surfactant complex as a reactive scaffold. A remarkable range of amphiphile-DNA structures (DNA-pyrene, DNA-triphenylphosphine, DNA-hydrocarbon, and DNA block copolymers) and a series of new brush-type DNA side-chain homopolymers with high DNA grafting density are produced efficiently. We believe that this method is an important breakthrough in developing a generalized approach to synthesizing functional DNA molecules for self-assembly and related technological applications.
Assuntos
DNA/química , Oligonucleotídeos/química , Compostos Orgânicos/química , Sequência de Bases , DNA/genética , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Conformação de Ácido Nucleico , Polimerização , Tensoativos/químicaRESUMO
The surface functionalization of fatty acid vesicles will allow their use as nanoreactors for complex chemistry. In this report, the tethering of several DNA conjugates to decanoic acid vesicles for molecular recognition and synthetic purposes was explored. Due to the highly dynamic nature of these structures, only one novel bola-amphiphile DNA conjugate could interact efficiently with or spontaneously pierce into the vesicle bilayers without jeopardizing their self-assembly or stability. This molecule was synthesized via a Cu(I)-catalyzed [3 + 2] azide-alkyne cycloaddition (click reaction), and consists of a single hydrocarbon chain of 20 carbons having on one end a triazole group linked to the 5'-phosphate of the nucleic acid and on the other side a hydroxyl-group. Its insertion was so effective that a fluorescent label on the DNA complementary to the conjugate could be used to visualize fatty acid structures.
Assuntos
DNA/química , Ácidos Decanoicos/química , Furanos/química , Piridonas/química , Alcinos/química , Azidas/química , Catálise , Química Click , Cobre/química , Corantes Fluorescentes/química , Interações Hidrofóbicas e Hidrofílicas , Membranas ArtificiaisRESUMO
Organic fluorophores, which are popular labels for microscopy applications, intrinsically suffer from transient and irreversible excursions to dark-states. An alternative to adding photostabilizers at high concentrations to the imaging buffer relies on the direct linkage to the fluorophore. However, the working principles of this approach are not yet fully understood. In this contribution, we investigate the mechanism of intramolecular photostabilization in self-healing cyanines, in which photodamage is automatically repaired. Experimental evidence is provided to demonstrate that a single photostabilizer, that is, the vitamin E derivative Trolox, efficiently heals the cyanine fluorophore Cy5 in the absence of any photostabilizers in solution. A plausible mechanism is that Trolox interacts with the fluorophore through intramolecular quenching of triplet-related dark-states, which is a mechanism that appears to be common for both triplet-state quenchers (cyclooctatetraene) and redox-active compounds (Trolox, ascorbic acid, methylviologen). Additionally, the influence of solution-additives, such as cysteamine and procatechuic acid, on the self-healing process are studied. The results suggest the potential applicability of self-healing fluorophores in stochastic optical reconstruction microscopy (STORM) with optical super-resolution. The presented data contributes to an improved understanding of the mechanism involved in intramolecular photostabilization and has high relevance for the future development of self-healing fluorophores, including their applications in various research fields.
RESUMO
PURPOSE: To describe intraocular clouding of silicone oil in the absence of emulsification. METHODS: Retrospective observational case series of patients who received silicone oil injections and developed silicone oil discoloration without emulsification after pars plana vitrectomy. Clinical examinations and physicochemical analyses were performed to find out the common cause for the opaque oil. RESULTS: Thirteen patients developed silicone oil discoloration after pars plana vitrectomy. It could be traced down that all patients had received silicone oil from one respective production batch. The silicone oil was removed as soon as possible after the changes were detected (range, 8-16 weeks). Gas chromatography flame ionization detector, size exclusion chromatography, and high-performance liquid chromatography analysis showed the absence of low-molecular-weight compounds in the opaque lot. Thermogravimetric analysis revealed the opaque lot was more temperature stable. During the follow-ups, no obvious retinal toxicity could be observed and best-recorded visual acuity improved considerably in 12 patients and was only limited by the underlying retinal pathologic conditions. CONCLUSION: This is the first report on opacification of intraocular silicone oil without emulsification. This discoloration of silicone oil may disturb vision and prevent proper fundus examination; however, it seems to be a nontoxic phenomenon without serious long-term consequences.
Assuntos
Descolamento Retiniano , Doenças Retinianas , Humanos , Descolamento Retiniano/cirurgia , Doenças Retinianas/etiologia , Estudos Retrospectivos , Óleos de Silicone/efeitos adversos , Vitrectomia/métodosRESUMO
Retinal eye diseases are the leading cause of blindness in the Western world. Up to date, the only efficient treatment for many retinal diseases consists of invasive intravitreal injections of highly concentrated drugs. Despite the fact that these injections are unpleasant for the patients, they potentially cause serious side effects, e.g., infections, bleeding within the eye or retinal detachment, especially when performed on a monthly basis, thus decreasing the injection frequency and lowering the desired drug dose. Therefore, a sustained released at the region of interest with a sustained release is desired. Recently, novel lipid-DNA nanoparticles (NPs) were shown to be an efficient drug delivery platform to the anterior segment of the eye. In this study, we investigated the distribution and tropism of the NPs when applied intravitreally, as a potential medication carrier to the posterior part of the eye. This technology is perfectly suited for the delivery of low molecular weight drugs to the back of the eye, which so far is greatly hindered by fast diffusion rates of the free drugs in the vitreous body and their intrinsically low retainability in ocular tissue. Excellent biodistribution, adherence and presence for up to five days was found for the different tested nanoparticles ex vivo and in vivo. In conclusion, our lipid-DNA based nanocarrier system was able to reach the retina within minutes and penetrate the retina providing potentially safe and long-term carrier systems for small molecules or nucleotide-based therapies.
RESUMO
Functional interfaces of biomolecules and inorganic substrates like semiconductor materials are of utmost importance for the development of highly sensitive biosensors and microarray technology. However, there is still a lot of room for improving the techniques for immobilization of biomolecules, in particular nucleic acids and proteins. Conventional anchoring strategies rely on attaching biomacromolecules via complementary functional groups, appropriate bifunctional linker molecules, or non-covalent immobilization via electrostatic interactions. In this work, we demonstrate a facile, new, and general method for the reversible non-covalent attachment of amphiphilic DNA probes containing hydrophobic units attached to the nucleobases (lipid-DNA) onto SAM-modified gold electrodes, silicon semiconductor surfaces, and glass substrates. We show the anchoring of well-defined amounts of lipid-DNA onto the surface by insertion of their lipid tails into the hydrophobic monolayer structure. The surface coverage of DNA molecules can be conveniently controlled by modulating the initial concentration and incubation time. Further control over the DNA layer is afforded by the additional external stimulus of temperature. Heating the DNA-modified surfaces at temperatures >80 °C leads to the release of the lipid-DNA structures from the surface without harming the integrity of the hydrophobic SAMs. These supramolecular DNA layers can be further tuned by anchoring onto a mixed SAM containing hydrophobic molecules of different lengths, rather than a homogeneous SAM. Immobilization of lipid-DNA on such SAMs has revealed that the surface density of DNA probes is highly dependent on the composition of the surface layer and the structure of the lipid-DNA. The formation of the lipid-DNA sensing layers was monitored and characterized by numerous techniques including X-ray photoelectron spectroscopy, quartz crystal microbalance, ellipsometry, contact angle measurements, atomic force microscopy, and confocal fluorescence imaging. Finally, this new DNA modification strategy was applied for the sensing of target DNAs using silicon-nanowire field-effect transistor device arrays, showing a high degree of specificity toward the complementary DNA target, as well as single-base mismatch selectivity.
Assuntos
Técnicas Biossensoriais/métodos , DNA/química , Interações Hidrofóbicas e Hidrofílicas , Sequência de Bases , DNA/genética , Eletrodos , Vidro/química , Ouro/química , Temperatura Alta , Modelos Moleculares , Conformação de Ácido Nucleico , Hibridização de Ácido Nucleico , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/genética , Semicondutores , Silício/química , Propriedades de SuperfícieRESUMO
Determination of the size distributions of natural polysaccharides is a challenging task. More advantageous for characterization are well-defined synthetic (hyper)-branched polymers. In this study we concentrated on synthetic amylopectin analogues in order to obtain and compare all available data for different distributions and size dependence of molecular weights. Two groups of well-defined synthetic branched polysaccharides were synthesized via an in vitro enzyme-catalyzed reaction using the enzyme phosphorylase b from rabbit muscle and Deinococcus geothermalis glycogen branching enzyme. Synthetic polymers had a tunable degree of branching (2%-13% determined via (1)H NMR) and a tunable degree of polymerization (30-350 determined indirectly via UV spectrometry). The systems used for separation and characterization of branched polysaccharides were SEC-DMSO/LiBr and multi detection (refractive index detector, viscosity detector, and multi angle light scattering detector) and SEC-water/0.02% NaN(3); and SEC-50 mM NaNO(3)/0.02% NaN(3) and multi detection. Additionally the side chain length distribution of enzymatically debranched polysaccharides was investigated by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) analysis. With this combination of characterization techniques, we were able not only to characterize the amylopectin analogues but also to solve parts of the molecular mechanism of their enzymatic polymerization. Moreover our materials showed potential to be standards in the field of natural polysaccharides characterization.
Assuntos
Enzima Ramificadora de 1,4-alfa-Glucana/metabolismo , Cromatografia em Gel/métodos , Fosforilase b/metabolismo , Polímeros/química , Polissacarídeos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Amilopectina/química , Animais , Deinococcus/enzimologia , Peso Molecular , Músculo Esquelético/citologia , Músculo Esquelético/enzimologia , Polimerização , CoelhosRESUMO
Glaucoma is the second leading cause of irreversible blindness worldwide. Among others, elevated intraocular pressure (IOP) is one of the hallmarks of the disease. Antiglaucoma drugs such as brimonidine can lower the IOP but their adherence to the ocular surface is low, leading to a low drug uptake. This results in a frequent dropping regime causing low compliance by the patients. Lipid DNA nanoparticles (NPs) have the intrinsic ability to bind to the ocular surface and can be loaded with different drugs. Here, we report DNA NPs functionalized for loading of brimonidine through specific aptamers and via hydrophobic interactions with double stranded micelles. Both NP systems exhibited improved affinity toward the cornea and retained release of the drug as compared to controls both in vitro and in vivo. Both NP types were able to lower the IOP in living animals significantly more than pristine brimonidine. Importantly, the brimonidine-loaded NPs showed no toxicity and improved efficacy and hence should improve compliance. In conclusion, this drug-delivery system offers high chances of an improved treatment for glaucoma and thus preserving vision in the aging population.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Tartarato de Brimonidina/uso terapêutico , DNA/química , Portadores de Fármacos/química , Glaucoma/tratamento farmacológico , Nanopartículas/química , Agonistas de Receptores Adrenérgicos alfa 2/química , Agonistas de Receptores Adrenérgicos alfa 2/toxicidade , Animais , Sequência de Bases , Tartarato de Brimonidina/química , Tartarato de Brimonidina/toxicidade , DNA/toxicidade , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Feminino , Interações Hidrofóbicas e Hidrofílicas , Pressão Intraocular/efeitos dos fármacos , Camundongos Endogâmicos DBA , Micelas , Nanopartículas/toxicidade , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/toxicidade , RatosRESUMO
Engineered viruses are finding an increasing number of applications in basic, translational research and materials science. Genetic and chemical engineering of capsids represents a key point for tailoring the properties of viral particles, but the synthetic efforts and limits accompanying these processes still hinder their usability. Here, a single-step highly selective biocatalytic functionalization approach is described, providing a general platform for virus-acrylate hybrid particles. The tobacco mosaic virus (TMV) and the bacteriophage M13 have been successfully modified via laccase induced free radical formation on the tyrosine residues through single electron oxidation as the initiating step and the free radicals subsequently react with acrylate-based monomers. This new approach can be extended to other biomolecular assemblies with surface exposed tyrosine residues, when the introduction of new functionalities is desired.
Assuntos
Bacteriófago M13/metabolismo , Capsídeo/metabolismo , Lacase/metabolismo , Vírus do Mosaico do Tabaco/metabolismo , Acrilatos/metabolismo , Biocatálise , Capsídeo/química , Microscopia Eletrônica de Transmissão , Oxirredução , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Tirosina/química , Tirosina/metabolismoRESUMO
We introduce a versatile carrier system for in vitro and in vivo immune stimulation based on soft matter DNA nanoparticles (NPs). The incorporation of lipid-modified nucleotides into DNA strands enables the formation of micelles of uniform size. In a single self-assembly step, the micelles can be equipped with immune adjuvant (CpG) motifs and fluorescent probes. The immunological effects of CpG confined at the NP surface were studied in a comprehensive manner in animal experiments. Dose-dependent activation of spleen dendritic cells (DCs) by CpG-conjugated NP was observed, which was accompanied by the pronounced up-regulation of co-stimulatory molecule and cytokine production.
Assuntos
Ilhas de CpG/genética , DNA/administração & dosagem , DNA/genética , Células Dendríticas/imunologia , Lipídeos/química , Nanocápsulas/química , Baço/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/química , Animais , Células Cultivadas , Citocinas/imunologia , Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Lipossomos/administração & dosagem , Lipossomos/química , Camundongos , Camundongos Endogâmicos C57BL , Baço/citologia , Baço/efeitos dos fármacos , Transfecção/métodosRESUMO
Lipidated DNAzymes or a lipidated Cu(II)-complex and lipidated aptamer sequences form supramolecular assemblies of micellar nucleoapzymes for the enhanced oxidation of dopamine to aminochrome. The catalytic functions of the micellar nucleoapzymes are attributed to the concentration of the substrate, using the aptamer units, in close proximity to the active sites.
Assuntos
Dopamina/química , Indolquinonas/química , Micelas , Catálise , OxirreduçãoRESUMO
The large multiprotein complex, photosystem I (PSI), which is at the heart of light-dependent reactions in photosynthesis, is integrated as the active component in a solid-state organic photovoltaic cell. These experiments demonstrate that photoactive megadalton protein complexes are compatible with solution processing of organic-semiconductor materials and operate in a dry non-natural environment that is very different from the biological membrane.
Assuntos
Fontes de Energia Bioelétrica , Eletrodos , Complexo de Proteína do Fotossistema I/química , Complexo de Proteína do Fotossistema I/efeitos da radiação , Semicondutores , Energia Solar , Transdutores , Transferência de Energia/efeitos da radiação , Desenho de Equipamento , Análise de Falha de Equipamento , Teste de MateriaisRESUMO
The field of DNA nanotechnology has progressed rapidly in recent years and hence a large variety of 1D-, 2D- and 3D DNA nanostructures with various sizes, geometries and shapes is readily accessible. DNA-based nanoobjects are fabricated by straight forward design and self-assembly processes allowing the exact positioning of functional moieties and the integration of other materials. At the same time some of these nanosystems are characterized by a low toxicity profile. As a consequence, the use of these architectures in a biomedical context has been explored. In this review the progress and possibilities of pristine nucleic acid nanostructures and DNA hybrid materials for drug delivery will be discussed. For the latter class of structures, a distinction is made between carriers with an inorganic core composed of gold or silica and amphiphilic DNA block copolymers that exhibit a soft hydrophobic interior.
Assuntos
DNA/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/química , Nanotecnologia/métodos , Animais , Sequência de Bases , Humanos , Modelos Moleculares , Nanoestruturas/ultraestrutura , Conformação de Ácido NucleicoRESUMO
Copper catalyzed azide-alkyne cycloaddition (CuAAC) was employed to synthesize DNA block copolymers (DBCs) with a range of polymer blocks including temperature-responsive poly(N-isoproylacrylamide) (poly(NIPAM)) and highly hydrophobic poly(styrene). Exceptionally high yields were achieved at low DNA concentrations, in organic solvents, and in the absence of any solid support. The DNA segment of the DBC remained capable of sequence-specific hybridization: it was used to assemble a precisely defined nanostructure, a DNA tetrahedron, with pendant poly(NIPAM) segments. In the presence of an excess of poly(NIPAM) homopolymer, the tetrahedron-poly(NIPAM) conjugate nucleated the formation of large, well-defined nanoparticles at 40 °C, a temperature at which the homopolymer precipitated from solution. These composite nanoparticles were observed by dynamic light scattering and cryoTEM, and their hybrid nature was confirmed by AFM imaging. As a result of the large effective surface area of the tetrahedron, only very low concentrations of the conjugate were required in order for this surfactant-like behavior to be observed.