DNA Self-assembly for Nanomedicine

Self-assembling DNA nanostructures based on rationally designed DNA branch junction molecules has recently led to the construction of patterned supramolecular structures with increased complexities. An intrinsic value of DNA tiles and patterns lies in their utility as molecular pegboard for deterministic positioning of molecules or particles with accurate distance and architectural control. This review will discuss the state-of-art developments in self-assembled DNA nanostructural system. Biomedical aspects of information guided DNA nanostructures will also be summarized. We illustrate both the use of simple DNA artworks for sensing, computation, drug delivery and the application of more complex DNA architectures as scaffolds for the construction of protein and nanoparticle arrays.     

Photosensitive pro-drug nanoassemblies harboring a chemotherapeutic dormancy function potentiates cancer immunotherapy

Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components—a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)—to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive “dormancy” characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved ¹O₂ generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.     

Self-assembled monolayers of long-chain xanthic acids on gold studied by voltammetry

A new method for the formation of xanthic acids H(CH₂)_nCS₂H (n=8, 10, 12) in a non-polar solvent from the corresponding potassium salts was developed. It was found that the xanthic acids spontaneously adsorb onto gold electrodes, via a mechanism that is proposed to be similar to the adsorption of thiols on gold surfaces. The xanthate modified gold electrodes were studied by cyclic voltammetry. It was found that the xanthate layers efficiently block the current from a ferro/ferri redox couple in aqueous solution. Studies of the electrochemical desorption of the xanthate layer supported the fact that xanthic acids spontaneously form a self-assembled monolayer on the electrode.     

Self-assembly of and charge transfer at N-docosyl-N′-methyl viologen on electrode surfaces

Self-assembled molecular films were formed on the electrode surfaces of glassy carbon (GC), platinum (Pt), gold, silver and indium–tin oxide in aqueous electrolyte solutions of N-docosyl-N′-methyl viologen (C₂₂VC₁). The temperature dependence of voltammetric responses showed a higher stability with higher surface coverage and with a Pt than a GC surface. Charge transfer reactions of the solution redox species of Ru(NH₃)₆³⁺ and Fe(CN)₆^4? at the irreversibly self-assembled C₂₂VC₁ ∣ GC interface were found to take place by an interplay of direct penetration of solution species through the self-assembled molecular layer of C₂₂VC₁ and of cross reaction between solution and surface bound redox agents.     

Electrochemical study of self-assembled monolayers of a β-cyclodextrin methyl sulfide covalently linked to anthraquinone

Self-assembled monolayers of a β-cyclodextrin with methyl sulfides on the primary sites of the molecule and mono-functionalized with anthraquinone on a secondary site have been formed on gold electrodes. The surface coverages obtained by electrochemistry are consistent with values reported previously or calculated for similar non-electroactive β-CD derivatives. The electron transfer rate constants vary markedly with pH, increasing rapidly between pH 7 and 9 to values of approximately 700–900 s^?1. These values are faster than reported previously for thiol derivatives of anthraquinone dispersed in an alkylthiol SAM matrix. Near pH 6, slow electron transfer is observed with a splitting into individual one-electron steps. Lowering the pH further results in very sluggish kinetics and indistinguishable peaks. Inclusion of naphthalene into the β-CD cavity appears to affect the anodic rate constant, and a small potential shift occurs. The efficient electron transfer of the anthraquinone spaced from the gold surface by a β-CD unit suggests promise for use of such molecules as ‘immobilized artificial enzymes’.     

Self-assembly of short peptides to form hydrogels: Design of building blocks,physical properties and technological applications

Hydrogels are unique supramolecular solid-like assemblies composed mainly of water molecules that are held by molecular networks. Physical hydrogels that are formed by a set of non-covalent interactions to establish a well-ordered scaffold devoid of any chemical cross-linking are especially intriguing for various biotechnological and medical applications. Peptides are particularly interesting building blocks of physical gels because of the role of polypeptides as structural elements in biological systems, the extensive ability for their chemical and biological decoration and functionalization, and the facile synthesis of natural and modified peptides. This review describes the assembly and properties of physical hydrogels that have been formed by the self-association of very simple peptide building blocks. Natural short peptides, as short as dipeptides, can form ordered gel assemblies. Moreover, in the case of N-terminal protection, even a protected amino acid can serve as an efficient hydrogelator. Further elucidation of hydrogelators’ assembly, as well as the characterization of their physical properties, can guide the rational design of building blocks for a desired application. The possible mechanism of self-assembly is discussed in line with the chemical nature of the short peptides. Different methods have been used to induce hydrogel assembly, which may significantly affect the mechanical characteristics of the resulting gels. Here, special emphasis is given to methods that allow either spatial control of hydrogel formation or modulation of physical properties of the gel. Finally, the parameters that influence hydrogelation are described, and insights for their design are provided.     

Facile route to versatile nanoplatforms for drug delivery by one-pot self-assembly

There is still unmet demand for developing powerful approaches to produce polymeric nanoplatforms with versatile functions and broad applications, which are essential for the successful bench-to-bedside translation of polymeric nanotherapeutics developed in the laboratory. We have discovered a facile, convenient, cost-effective and easily scalable one-pot strategy to assemble various lipophilic therapeutics bearing carboxyl groups into nanomedicines, through which highly effective cargo loading and nanoparticle formation can be achieved simultaneously. Besides dramatically improving water solubility, the assembled nanopharmaceuticals showed significantly higher bioavailability and much better therapeutic activity. These one-pot assemblies may also serve as nanocontainers to effectively accommodate other highly hydrophobic drugs such as paclitaxel (PTX). PTX nanomedicines thus formulated display strikingly enhanced in vitro antitumor activity and can reverse the multidrug resistance of tumor cells to PTX therapy. The special surface chemistry offers these assembled entities the additional capability of efficiently packaging and efficaciously transfecting plasmid DNA, with a transfection efficiency markedly higher than that of commonly used positive controls. Consequently, this one-pot assembly approach provides a facile route to multifunctional nanoplatforms for simultaneous delivery of multiple therapeutics with improved therapeutic significance.     

Introducing a combinatorial DNA-toolbox platform constituting defined protein-based biohybrid-materials

The access to defined protein-based material systems is a major challenge in bionanotechnology and regenerative medicine. Exact control over sequence composition and modification is an important requirement for the intentional design of structure and function. Herein structural- and matrix proteins provide a great potential, but their large repetitive sequences pose a major challenge in their assembly. Here we introduce an integrative “one-vector-toolbox-platform” (OVTP) approach which is fast, efficient and reliable. The OVTP allows for the assembly, multimerization, intentional arrangement and direct translation of defined molecular DNA-tecton libraries, in combination with the selective functionalization of the yielded protein-tecton libraries. The diversity of the generated tectons ranges from elastine-, resilin, silk- to epitope sequence elements. OVTP comprises the expandability of modular biohybrid-materials via the assembly of defined multi-block domain genes and genetically encoded unnatural amino acids (UAA) for site-selective chemical modification. Thus, allowing for the modular combination of the protein-tecton library components and their functional expansion with chemical libraries via UAA functional groups with bioorthogonal reactivity. OVTP enables access to multitudes of defined protein-based biohybrid-materials for self-assembled superstructures such as nanoreactors and nanobiomaterials, e.g. for approaches in biotechnology and individualized regenerative medicine.     

Introduction to nanocoatings produced by layer-by-layer (LbL) self-assembly

Studies on the adsorption of oppositely charged colloidal particles ultimately resulted in multilayered polyelectrolyte self-assembly. The inception of layer-by-layer constructed particles facilitated the production of multifunctional, stimuli-responsive carrier systems. An array of synthetic and natural polyelectrolytes, metal oxides and clay nanoparticles is available for the construction of multilayered nanocoats on a multitude of substrates or removable cores. Numerous substrates can be encapsulated utilizing this technique including dyes, enzymes, drugs and cells. Furthermore, the outer surface of the particles presents and ideal platform that can be functionalized with targeting molecules or catalysts. Some processing parameters determining the properties of these successive self-assembly constructs are the surface charge density, coating material concentration, rinsing and drying steps, temperature and ionic strength of the medium. Additionally, the simplicity of the layer-by-layer assembly technique and the availability of established characterization methods, render these constructs extremely versatile in applications of sensing, encapsulation and target- and trigger-responsive drug delivery.     

仿生构建具有一氧化氮自催化生成功能的人工血管材料

目的 利用有机硒催化一氧化氮(No)供体释放NO的能力设计一种新型人工血管支架材料。方法固载有机硒催化剂的聚乙烯亚胺( SePEI)作为聚阳离子,与聚阴离子聚谷氨酸(PGA)在静电纺丝得到的纳米纤维支架聚己内酯(PCL)表面层层自组装,用紫外和原子吸收进行了定性和定量的表征层层自组装结构;在还原型谷胱甘肽(GSH)的存...