Nano Assembly Research Articles

Novel Nanoassemblies Composed of Squalenoyl−Paclitaxel Derivatives: Synthesis, Characterization, and Biological Evaluation

Using the anticancer compound paclitaxel as a model drug, this study investigates the potential of the squalenoylation technology (i.e., bioconjugation with the natural lipid squalene) in addressing the drug ability and delivery issues of poorly soluble therapeutic agents. In this view, a variety of novel squalene-based prodrugs of the anticancer compound paclitaxel were synthesized, which produced nanoparticles in water. These prodrugs were obtained by covalent coupling of the paclitaxel 2'-hydroxyl group as direct ester, as well as with a succinate or a diglycolate ester as cleavable linker to the 1,1',2-tris-norsqualenoic acid. The hydrophilicity of these paclitaxel bioconjugates was increased by placing poly(ethylene glycol) chains of different lengths between paclitaxel and the squalenoyl moiety. All these prodrugs self-assembled into nanosized aggregates in aqueous solution as characterized by dynamic light scattering, atomic force microscopy, and transmission electron microscopy. The critical aggregation concentration was very low, ranging from 0.09 to 0.4 mg/L. Zeta potential measurements revealed that all squalenoyl-paclitaxel nanoassemblies (NA) held a global negative charge and appeared stable in water for several weeks as determined by particle size measurement. The release of paclitaxel from NA was evaluated in different conditions and in the presence of serum and depended on the nature of the linker used. Preliminary biological assessment showed that these squalenoyl-paclitaxel NA induced the formation of microtubule bundles in HT-29 and KB-31 cells, and additionally displayed notable cytotoxicity on a lung tumor cell line. Furthermore, the cytotoxic activity of these different prodrugs correlated closely with the observed linker stability. Overall, the squalenoylation nanotechnology opens up interesting perspectives for the development of injectable prodrugs of poorly soluble therapeutic compounds by addressing the associated physicochemical and biopharmaceutical challenges.

The synthesis and crystallization mechanism of protein-conjugated silver sulfide nanowires with hierarchical structure

The Bovine serum albumin (BSA)-conjugated silver sulfide (Ag 2S) nanowires with hierarchical structure were prepared under the gentle conditions by using BSA as the matrix and with the assistance of anodic aluminum oxide (AAO) templates. The high-resolution transmission electron microscope (HRTEM) showed the nanowires were with 50 nm in the diameter and several micrometers in the length and composed of nanoparticles with 10 nm in the diameter. The real-time observation by transmission electron microscope (TEM) displayed that the nano assemblies were formed from the smaller building blocks step by step.

Extracellular-protein-enhanced cellular uptake of squalenoyl gemcitabine from nanoassemblies

The mechanism by which the squalenoyl prodrug of the anticancer agent gemcitabine was transferred from its nanoassemblies (NAs) to cancer cell lines was investigated by means of in vitro cell uptake experiments. The endocytosis of the NAs was proven not to constitute the main uptake pathway of the squalenoyl gemcitabine bioconjugate (SQdFdC), which indicated that the uptake occurred by passive diffusion. On the contrary, the cell uptake was found importantly influenced by the concentration and nature of the extracellular proteins: it was very limited in protein-free media, reached a maximum at intermediate protein concentrations, and then strongly diminished at high extracellular protein concentrations. This phenomenon was demonstrated not to stem from the alteration of the colloidal stability of the NAs that could have occurred upon modification of the protein concentration. Our results indicated that SQdFdC cell uptake happened through an albumin-enhanced diffusion of molecular SQdFdC across the aqueous medium, rather than through a direct interaction between NAs and cells. Noteworthy, in our in vitro experimental conditions, lipoproteins were detrimental to the cell uptake because they trapped the available SQdFdC molecules without mediating their diffusive capture by the cells.

DNAやペプチドの自己集合によるナノバイオ分子システムの構築

In biological system, various nano–assemblies are formed by self–assembly of proteins with high symmetric ternary structures. For example, dodecahedral internal skeleton of tomato bushy stunt virus is self–assembled from C3–symmetric β–sheet subunits. Inspired by such self–assembly process, we have developed a novel strategy for construction of spherical assemblies consisting of biomacromolecules such as DNA and peptides. DNA three–way junctions bearing self–complementary sticky–ends were self–assembled into nanometer to micrometer sized spherical structures depending on the concentration. The three–way component design was extended to the design of the artificial C3–symmetric conjugate which contains three β–sheet–forming peptides FKFEFKFE. Radial–type Trigonal–FKFE self–assembled into nanocapsules with the size of 20 nm. In contrast, wheel–type Trigonal–FKFE self–assembled into nanofibers with uniform width (3 nm). Recently, we designed T–shaped C3–symmetric peptide conjugate Trigonal–glutathiones (TG). TG self–assembled into soft nanospheres with the size of about 100—250 nm, whose size was little affected by the concentration.

Fluorescent and triplet state photoactive J-type phthalocyanine nano assemblies: controlled formation and photosensitizing properties

Cofacial J type nano aggregates, which are both fluorescent and triplet state photoactive, were formed in chloroform via multiple O → Zn2+ coordination bonds between molecules of ZnPc(α-OPh)4, i.e. tetra(α-phenoxy) zinc phthalocyanine. Non photoactive H aggregates, on the other hand, were observed in DMF–water mixtures. The formation, structure and bonding of the J aggregates were examined by TEM, electronic absorption and fluorescence methods. Photophysical studies revealed that the J-aggregates have narrowed absorption and emission bands with peak wavelengths at 740 and 751 nm, which are 50 nm and 43 nm red shifted from the values of the monomers, respectively. The fluorescence decay of the J aggregates is monoexponential with a long lifetime of 2.41 ns, in contrast to J aggregates of other dyes that usually exhibit much shorter, while widely distributed, lifetimes in the ps scale due to the loosely formed structures. The J aggregates emit fluorescence with an efficiency as high as 50% of its monomer. The laser flash photolysis study revealed that both the triplet state and anion species were generated upon photo excitation. The triplet state was formed in a quantum yield of 0.20 and its lifetime is 11 μs, which makes it sufficiently effective to transfer triplet energy and produce singlet oxygen with a yield of 0.23. The J aggregates represent a new category of nano assemblies that have the potential to be utilized in a variety of optoelectronic devices and photodynamic therapy of tumors.

Towards understanding biomineralization: calcium phosphate in a biomimetic mineralization process

Abstract Biomineralization processes result in organic/inorganic hybrid materials with complex shapes, hierarchical structures, and superior material properties. Recent developments in biomineralization and biomaterials have demonstrated that calcium phosphate particles play an important role in the formation of hard tissues in nature. In this paper, current concepts in biomineralization, such as nano assembly, biomimetic shell structure, and their applications are introduced. It is confirmed experimentally that enamel- or bone-liked apatite can be achieved by oriented aggregations using nano calcium phosphates as starting materials. The assembly of calcium phosphate can be either promoted or inhibited by different biomolecules so that the kinetics can be regulated biologically. In this paper, the role of nano calcium phosphate in tissue repair is highlighted. Furthermore, a new, interesting result on biomimetic mineralization is introduced, which can offer an artificial shell for living cells via a biomimetic method.

Nanoessence: God, the first nano assembler

The Nanoessence project aims to examine life at a sub-cellular level, re-examining space and scale within the human context. A single HaCat skin cell is analysed with an Atomic Force Microscope (AFM) to explore comparisons between, life and death at a nano level. The humanistic discourse concerning life is now being challenged by nanotechnological research that brings into question the concepts of what constitutes living. The Nanoessence project research is based on data gathered as part of a residency at SymbioticA, Centre of Excellence in Biological Arts, University of Western Australia and the Nanochemistry Research Institute, (NRI) Curtin University of Technology. The space of the body can be seen at an atomic level as having no defining boundaries. More generally, molecular self-assembly seeks to use concepts of supramolecular chemistry, and molecular recognition in particular, to cause single-molecule components to automatically arrange themselves into some useful conformation (reference Wikipedia). Nano assembly, or bottom-up approach, is the construction of a supramolecular chemistry by the assembly of nanoscopic particles, or even atoms and molecules. The proposal for nanotechnology to reshape nature atom by atom develops an interesting debate as to the constitution of life. The Nanoessence project aims to construct a physical experience to examine this scientific and metaphysical world. Nanoessence is an interactive audio-visual installation. In the Nanoessence installation the viewer will interface with the visual and sonic presentation through his or her own breath. In the context of the project breath has a strong conceptual and metaphorical link to a Biblical inception of life. The project attempts to maintain a high quality of authentic data to engage the viewer in a sensorial qualitative experience of quantitative data.

Effect of Headgroup Chirality in Nanoassemblies. Part 1. Self-Assembly of d-Isoascorbic Acid Derivatives in Water

L-(+)-Ascorbic acid and D-(-)-isoascorbic acid are epimers, with an opposite configuration at the C5 stereogenic chiral center. Single-chained surfactants that carry a L-ascorbic or d-isoascorbic acid residue as hydrophilic headgroup and an alkanoate tail as hydrophobic chain were synthesized. We refer to these as L-ASCn and D-ASCn, with n=8, 10, or 12. The role of the headgroup configuration in determining the nature of both the pure compounds and their nano assembly in aqueous dispersions were studied. Surface tension, infrared spectroscopy, differential scanning calorimetry, conductivity, small-angle X-ray scattering, and wide-angle X-ray diffractometry were used to characterize surfactant properties as a function of temperature and concentration. The L and D headgroup forms have significantly different hydration. This greatly affects the structure and stability of the aggregates in the micellar and coagel states.

2A1-J05 細胞ナノシステムによるバイオハイブリッドナノマシン構築 : ナノマシンの自己組織的組み立てに向けた細胞移動の制御

Cell driven construction of bionic nano/micro systems had been conceptualized to embed biological self-contain nano mechanochemical systems in nano machine. Cell skeletal filaments are controlled by membrane protein reactions which are related to interaction between these and external bioactive patterns with nanostructures. So, we evaluated the migration behavior on various pattern of MPC treatment. The liner pattern performed higher deviation of displacements in cell migration than the circular pattern. These cellular behaviors would contribute controlling of molecular reaction driven nano assembly mechanism in the biological molecular system of cells.

Mechanisms of the Assembly of Nano- and Microparticle Two-Dimensional Structures in a Wedge Film

When a drop of colloidal suspension is deposited on a smooth solid surface, the colloidal spheres self-assemble into two-dimensional ordered structures in the three-phase contact region (i.e., wedg...

Near-term nanotechnology: the molecular fabrication of nanostructured materials

The remarkably short timescales commonly predicted for achieving full molecular nanotechnology (MNT) are not realistic, as an enormous investment must be made up-front for a distant and ill-defined payoff. The reason is that technology, per se, is not an economic driver; economics instead drives technology. Hence, markets that could motivate the ongoing, incremental development of MNT must be sought. Such markets exist: they fundamentally consist of the molecular assembly of nano structured materials such as semipermeable membranes, catalysts, perfect crystalline fibres, and others. Although in theory atomically precise, such materials have no molecular moving parts and thus will be both easier to build and more robust. Some of these applications (e.g. catalysis), moreover, have huge, mature markets. Once a demand is established, further incremental development of primitive molecular assemblers, or `molecular looms', might then justify the analogies with the explosive development of computer hardware over the last few decades. Finally, the fact that many such applications are likely to be rendered obsolete by full MNT is irrelevant to their interim value as technology drivers.