Cooperative Macromolecular Self-Assembly toward Polymeric Assemblies with Multiple and Bioactive Functions

ConspectusIn the past decades, polymer based nanoscale polymeric assemblies have attracted continuous interest due to their potential applications in many fields, such as nanomedicine. Many efforts have been dedicated to tailoring the three-dimensional architecture and the placement of functional groups at well-defined positions within the polymeric assemblies, aiming to augment their function. To achieve such goals, in one way, novel polymeric building blocks can be designed by controlled living polymerization methodology and advanced chemical modifications. In contrast, by focusing on the end function, others and we have been practicing strategies of cooperative self-assembly of multiple polymeric building blocks chosen from the vast library of conventional block polymers which are easily available. The advantages of such strategies lie in the simplicity of the preparation process and versatile choice of the constituent polymers in terms of their chemical structure and functionality as well as the fact that cooperative self-assembly based on supramolecular interactions offers elegant and energy-efficient bottom-up strategies. Combination of these principles has been exploited to optimize the architecture of polymeric assemblies with improved function, to impart new functionality into micelles and to realize polymeric nanocomplexes exhibiting functional integration, similar to some natural systems like artificial viruses, molecular chaperones, multiple enzyme systems, and so forth.In this Account, we shall first summarize several straightforward designing principles with which cooperative assembly of multiple polymeric building blocks can be implemented, aiming to construct polymeric nanoassemblies with hierarchal structure and enhanced functionalities. Next, examples will be discussed to demonstrate the possibility to create multifunctional nanoparticles by combination of the designing principles and judiciously choosing of the building blocks. We focus on multifunctional nanoparticles which can partially address challenges widely existing in nanomedicine such as long blood circulation, efficient cellular uptake, and controllable release of payloads. Finally, bioactive polymeric assemblies, which have certain functions closely mimicking those of some natural systems, will be used to conceive the concept of functional integration

Stabilization of Multimeric Enzymes against Heat Inactivation by Chitosan-<i>graft</i>-poly(<i>N</i>‑isopropylacrylamide) in Confined Spaces

The inactivation of multimeric enzymes is a more complicated process compared with that of monomeric enzymes. Stabilization of multimeric enzymes is regarded as a challenge with practical values in enzyme technology. Temperature-sensitive copolymer chitosan-<i>graft</i>- poly­(<i>N</i>-isopropylacrylamide) was synthesized and encapsulated with multimeric enzymes in the confined spaces constructed by the W/O microemulsion. In this way, the quaternary structures of multimeric enzymes are stabilized and the thermal stabilities of them are enhanced. The whole process was studied and discussed. This method, which works well for both glucose oxidase and catalase, can be developed as a general protection strategy for multimeric enzymes

Self-Etching of Metal–Organic Framework Templates during Polydopamine Coating: Nonspherical Polydopamine Capsules and Potential Intracellular Trafficking of Metal Ions

Traditionally, containers made from steel or other metals are not good for making tea, probably due to the fact that polyphenol components in tea can chelate with metal ions. A similar reason might stand behind the observations as reported herein. During the coating of well-defined metal–organic framework (MOF) crystalline particles with polydopamine (PDA) via pH-induced self-polymerization of dopamine, we found that MOF templates automatically etch off during the coating, giving rise to nonspherical PDA capsules that inherit the morphologies of the templates. Such self-etching of MOF templates is ascribed to the chelation of the metal nodes of the MOFs by the catechol moieties in the PDA layer. In addition, the self-etching of the zeolitic imidazolate framework-8 (ZIF-8) with a truncated cubic shape probably follows a crystalline facet-dependent fashion, resulting in intermediate yolk–shell structures with ZIF-8 cargos of various shapes inside a highly biocompatible PDA shell. Incubation of such intermediate hybrid particles with the cancerous HeLa cell line leads to pronounced cytotoxicity, which is tentatively connected with the cellular internalization of the ZIF@PDA nanoparticles because of the cell affinity of the PDA layer. Subsequently, the continuous release of Zn²⁺ by the self-etching of the encapsulated ZIF-8 inside the cell increases intracellular Zn²⁺ to a harmful level. Therefore, intracellular delivery of metal ions is probably realized, which might offer a novel way for cancer therapy

Thermoresponsive Chiral to Nonchiral Ordering Transformation in the Nematic Liquid-Crystal Phase of Rodlike Viruses: Turning the Survival Strategy of a Virus into Valuable Material Properties

The current work investigates the thermoresponsive in situ chiral to nonchiral ordering transformation of a rodlike virus in the naturally assembled statethe chiral nematic liquid crystal (CLC) phase. We take this as an elegant example of reconfigurable self-assembly, through which it is possible to realize in situ transformation from one assembled state to another without disrupting the preformed assembly in general or going through a secondary assembling procedure of the disassembled building blocks. The detailed investigation presented here reveals many unique characteristics of the thermoresponsive 3D chiral ordering of rodlike viruses induced by heat stress. The chiral to nonchiral ordering transformation is highly reversible in the temperature range of up to 60 °C and can be repeated many times. There exists a critical temperature around 40 °C which is independent of the ionic strength and virus concentration. Such reconfigurable ordering in the CLC phase stems from the intrinsic structure change of constituent coat proteins without disrupting the structural integrity of the virus, as revealed by three analytical techniques targeting levels ranging from the molecular, secondary conformation of the constituent proteins to the whole single virus, respectively. Such structural flexibility, also termed polymorphism, is relative to the survival strategies of a biological organism such as the virus and can be transformed into very precious material properties. The potential of the virus-based CLC phase as the chiral matrix to regulate chiro-optical properties of gold nanorods is also presented

Thermoresponsive Chiral to Nonchiral Ordering Transformation in the Nematic Liquid-Crystal Phase of Rodlike Viruses: Turning the Survival Strategy of a Virus into Valuable Material Properties

The current work investigates the thermoresponsive in situ chiral to nonchiral ordering transformation of a rodlike virus in the naturally assembled statethe chiral nematic liquid crystal (CLC) phase. We take this as an elegant example of reconfigurable self-assembly, through which it is possible to realize in situ transformation from one assembled state to another without disrupting the preformed assembly in general or going through a secondary assembling procedure of the disassembled building blocks. The detailed investigation presented here reveals many unique characteristics of the thermoresponsive 3D chiral ordering of rodlike viruses induced by heat stress. The chiral to nonchiral ordering transformation is highly reversible in the temperature range of up to 60 °C and can be repeated many times. There exists a critical temperature around 40 °C which is independent of the ionic strength and virus concentration. Such reconfigurable ordering in the CLC phase stems from the intrinsic structure change of constituent coat proteins without disrupting the structural integrity of the virus, as revealed by three analytical techniques targeting levels ranging from the molecular, secondary conformation of the constituent proteins to the whole single virus, respectively. Such structural flexibility, also termed polymorphism, is relative to the survival strategies of a biological organism such as the virus and can be transformed into very precious material properties. The potential of the virus-based CLC phase as the chiral matrix to regulate chiro-optical properties of gold nanorods is also presented

Reversible Interactions of Proteins with Mixed Shell Polymeric Micelles: Tuning the Surface Hydrophobic/Hydrophilic Balance toward Efficient Artificial Chaperones

Molecular chaperones can elegantly fine-tune its hydrophobic/hydrophilic balance to assist a broad spectrum of nascent polypeptide chains to fold properly. Such precious property is difficult to be achieved by chaperone mimicking materials due to limited control of their surface characteristics that dictate interactions with unfolded protein intermediates. Mixed shell polymeric micelles (MSPMs), which consist of two kinds of dissimilar polymeric chains in the micellar shell, offer a convenient way to fine-tune surface properties of polymeric nanoparticles. In the current work, we have fabricated ca. 30 kinds of MSPMs with finely tunable hydrophilic/hydrophobic surface properties. We investigated the respective roles of thermosensitive and hydrophilic polymeric chains in the thermodenaturation protection of proteins down to the molecular structure. Although the three kinds of thermosensitive polymers investigated herein can form collapsed hydrophobic domains on the micellar surface, we found distinct capability to capture and release unfolded protein intermediates, due to their respective affinity for proteins. Meanwhile, in terms of the hydrophilic polymeric chains in the micellar shell, poly­(ethylene glycol) (PEG) excels in assisting unfolded protein intermediates to refold properly via interacting with the refolding intermediates, resulting in enhanced chaperone efficiency. However, another hydrophilic polymer-poly­(2-methacryloyloxyethyl phosphorylcholine) (PMPC) severely deteriorates the chaperone efficiency of MSPMs, due to its protein-resistant properties. Judicious combination of thermosensitive and hydrophilic chains in the micellar shell lead to MSPM-based artificial chaperones with optimal efficacy

Pure Anisotropic Hydrogel with an Inherent Chiral Internal Structure Based on the Chiral Nematic Liquid Crystal Phase of Rodlike Viruses

Imparting ordered structures into otherwise amorphous hydrogels is expected to endow these popular materials with novel multiple-stimuli responsiveness that promises many applications. The current contribution reports a method to fabricate pure polymeric hydrogels with an inherent chiral internal structure by templating on the chiral nematic liquid crystal phase of a rodlike virus. A method was developed to form macroscopically homogeneous chiral templates by confinement induced self-assembly in the presence of monomers, cross-linkers and initiators. Polymerization induced gelation was performed without perturbing the elegant 3D chiral organization of the rodlike virus bearing double bonds. Furthermore, a suitable method was found to remove the organic virus template while keeping the desired polymeric replica intact, resulting in a pure polymeric hydrogel with a unique internal chiral feature that originates from the 3D chiral ordering of the cylindrical pores left by the virus. Multiple-stimuli responsiveness has been demonstrated and can be quantified by the change of the pitch of the chiral feature. The chiral structure endows the otherwise featureless hydrogel with a unique material property that might be used as a readout signal for sensing and acts as the basis for responsive, biomimetic nanostructured materials

Pure Anisotropic Hydrogel with an Inherent Chiral Internal Structure Based on the Chiral Nematic Liquid Crystal Phase of Rodlike Viruses

Imparting ordered structures into otherwise amorphous hydrogels is expected to endow these popular materials with novel multiple-stimuli responsiveness that promises many applications. The current contribution reports a method to fabricate pure polymeric hydrogels with an inherent chiral internal structure by templating on the chiral nematic liquid crystal phase of a rodlike virus. A method was developed to form macroscopically homogeneous chiral templates by confinement induced self-assembly in the presence of monomers, cross-linkers and initiators. Polymerization induced gelation was performed without perturbing the elegant 3D chiral organization of the rodlike virus bearing double bonds. Furthermore, a suitable method was found to remove the organic virus template while keeping the desired polymeric replica intact, resulting in a pure polymeric hydrogel with a unique internal chiral feature that originates from the 3D chiral ordering of the cylindrical pores left by the virus. Multiple-stimuli responsiveness has been demonstrated and can be quantified by the change of the pitch of the chiral feature. The chiral structure endows the otherwise featureless hydrogel with a unique material property that might be used as a readout signal for sensing and acts as the basis for responsive, biomimetic nanostructured materials

Thermoresponsive Chiral to Nonchiral Ordering Transformation in the Nematic Liquid-Crystal Phase of Rodlike Viruses: Turning the Survival Strategy of a Virus into Valuable Material Properties

The current work investigates the thermoresponsive in situ chiral to nonchiral ordering transformation of a rodlike virus in the naturally assembled statethe chiral nematic liquid crystal (CLC) phase. We take this as an elegant example of reconfigurable self-assembly, through which it is possible to realize in situ transformation from one assembled state to another without disrupting the preformed assembly in general or going through a secondary assembling procedure of the disassembled building blocks. The detailed investigation presented here reveals many unique characteristics of the thermoresponsive 3D chiral ordering of rodlike viruses induced by heat stress. The chiral to nonchiral ordering transformation is highly reversible in the temperature range of up to 60 °C and can be repeated many times. There exists a critical temperature around 40 °C which is independent of the ionic strength and virus concentration. Such reconfigurable ordering in the CLC phase stems from the intrinsic structure change of constituent coat proteins without disrupting the structural integrity of the virus, as revealed by three analytical techniques targeting levels ranging from the molecular, secondary conformation of the constituent proteins to the whole single virus, respectively. Such structural flexibility, also termed polymorphism, is relative to the survival strategies of a biological organism such as the virus and can be transformed into very precious material properties. The potential of the virus-based CLC phase as the chiral matrix to regulate chiro-optical properties of gold nanorods is also presented

Ellipsoidal Colloids with a Controlled Surface Roughness via Bioinspired Surface Engineering: Building Blocks for Liquid Marbles and Superhydrophobic Surfaces

Understanding the important role of the surface roughness of nano/colloidal particles and harnessing them for practical applications need novel strategies to control the particles’ surface topology. Although there are many examples of spherical particles with a specific surface roughness, nonspherical ones with similar surface features are rare. The current work reports a one-step, straightforward, and bioinspired surface engineering strategy to prepare ellipsoidal particles with a controlled surface roughness. By manipulating the unique chemistry inherent to the oxidation-induced self-polymerization of dopamine into polydopamine (PDA), PDA coating of polymeric ellipsoids leads to a library of hybrid ellipsoidal particles (PS@PDA) with a surface that decorates with nanoscale PDA protrusions of various densities and sizes. Together with the advantages originated from the anisotropy of ellipsoids and rich chemistry of PDA, such a surface feature endows these particles with some unique properties. Evaporative drying of fluorinated PS@PDA particles produces a homogeneous coating with superhydrophobicity that arises from the two-scale hierarchal structure of microscale interparticle packing and nanoscale roughness of the constituent ellipsoids. Instead of water repelling that occurs for most of the lotus leaf-like superhydrophobic surfaces, such coating exhibits strong water adhesion that is observed with certain species of rose pedals. In addition, the as-prepared hybrid ellipsoids are very efficient in preparing liquid marble-isolated droplets covered with solid particles. Such liquid marbles can be placed onto many surfaces and might be useful for the controllable transport and manipulation of small volumes of liquids