Controlled Preparation And Bioapplication Of Functional Supramolecular Assembling Systems

Supramolecular chemistry referring to the chemistry beyond the molecule, aims at constructing highly complex, functional supramolecular aggregates from molecular components held together through intermolecular noncovalent forces. As a newly emerging interdisciplinary subject, supramolecular chemistry has recently attracted much attention in a wide range of fields including material science, nanoscience, information science, and life science. Up to now, a remarkable progress has been achieved in supramolecular chemistry. However, the majority of relevant studies mainly focus on the morphology control of supramolecular systems, whereas less research attention is given to the functionalization of supramolecular systems and structure-function relationship, thereby greatly limiting their applications in various fields. Therefore, how to design and develop supramolecular systems with controlled structure and tunable function for various applications based on reversible characteristics of noncovalent interactions, is still the frontier scientific issue in the field of supramolecular chemistry. In this dissertation, a series of supramolecular assembling systems with distinct structures and functions have been successfully fabricated by using different noncovalent strategies. As a result, these supramolecular assembling systems not only display specific functions, but also have great potential for a variety of biomedical applications including gene delivery, bioimaging, and biomimetic chemistry. This dissertation can be divided into six major sections, and the main research contents and conclusions are shown as follows: 1. Self-assembly and optical properties of a porphyrin-based amphiphileHitherto, most of studies in porphyrin chemistry have mainly focused on the design and construction of various well-defined porphyrin-based nanostructures, while few studies devoted to expatiating on the effect of aggregated structure on optical properties. Thus, it is necessary to explore the structure-property relationship of porphyrin-based nanomaterials to push forward the development of porphyrin chemistry. Herein, we report a porphyrin-based amphiphile with unique chemical structure and amphiphilic nature, which exhibits various morphologies via self-assembly in different solvents, thus bringing distinct optical properties. This porphyrin-based amphiphile as a multivalent guest is capable of complexing with α-cyclodextrin to form supramolecular inclusion complexes, and then further self-organizes into well-defined spherical nanoparticles in aqueous medium accompanied by excellent optical properties. In addition, this amphiphile and its assemblies show dynamic/switchable morphology and optical properties in response to light. Furthermore, the effect of self-assembly behavior on optical properties of this amphiphile has been well investigated to get a better understanding on the structure-performance relationship. 2. Photo-reversible supramolecular hyperbranched polymersThe reversibility of noncovalent interactions endows the resultant supramolecular polymers with the ability to undergo reversible switching of structure and properties under exposure to various external stimuli in contrast to conventional covalent polymers, thereby offering a flexible and robust platform for the design and development of smart supramolecular polymeric materials. In this chapter, we have constrcuted a novel class of A2-B3 type photoreversible supramolecular hyperbranched polymers through the reversible host-guest interactions between azobenzene dimer and β-cyclodextrin trimer. As expected, the resulting supramolecular polymers not only display well-defined branched structure and excellent optical properties, but also can achieve reversible polymerization and depolymerization upon alternating ultraviolet and visible light irradiation. Furthermore, their branched structure and optical properties can be switched reversibly by alternative irradiation with ultraviolet and visible light through the reversible association and disassociation of the non-covalent connection in the backbone. Therefore, this novel class of photoreversible supramolecular hyperbranched polymers has great potential as promising fluorescent materials and self-healing materials in near future. 3. Vesicular system with jellyfish-like breathing and light-emitting behaviorIn nature, there are a large number of cellular processes or living organisms that have a cooperative function expression during the membrane deformation. Up to date, all reported cytomimetic processes are limited to morphological transformations, while no function has been generated during these processes. Inspired by jellyfish, we report on a novel class of smart “breathing” vesicles accompanied with reversible on-off switchable fluorescence behavior. This biomimetic vesicle system has been prepared through the aqueous self-assembly of an amphiphilic block copolymer composed of many dimethylamino azobenzene chromophores. The resulting vesicles can undergo a p H-induced breathing behavior accompanied with the swelling and shrinkage of the vesicles. For the breathing-in process in an acidic condition, the vesicle swells in size and thins in the wall accompanied with the quenching of the fluorescence due to the protonation process; Inversely, for the breathing-out process in an alkaline condition, the vesicle shrinks in size and thickens in the wall accompanied with the strong green fluorescence recovery due to the deprotonation process. Such a cooperative membrane deformation and light-emitting behavior during the breathing process is similar to that of the jellyfish. In addition, this vesicle system also presents several interesting properties including the aggregation-induced emission(AIE) behaviors, visible light-induced trans-to-cis photoisomerization, and photoisomerization-induced reversible fluorescence decrease and recovery behaviors. Therefore, this work may extend the cytomimetic chemistry from the mere membrane morphological transformation into a combination of the cytomimetic morphology with the cooperative function expression. 4. Supramolecular fluorescent nanoparticles for bioimagingπ-π interactions of π-conjugated building blocks in aqueous medium frequently lead to the formation of the irregular supramolecular aggregates or insoluble precipitates with self-quenching fluorescence. The utilization of noncovalent interactions to prepare well-defined supramolecular nanostructures with highly fluorescent performance through self-assembly in water is a great challenge. Herein, a promising class of calcein-based supramolecular fluorescent nanoparticles, by a combination of excellent fluorescent properties with smart targeting ability for cancer-specific delivery, has been successfully fabricated using a “bricks and mortar” strategy. Through tuning the molar ratio of adamantane-functionalized calcein/β-cyclodextrin-grafted branched polyethylenimine, the size of the resulting supramolecular fluorescent nanoparticles can be effectively controlled. Notably, the β-cyclodextrin/adamantane host-guest interaction dramatically suppresses the π-π stacking and fluorescence self-quenching of calcein chromophores in water, thereby resulting in the formation of highly fluorescent nanostructures. Moreover, the introduction of the folate receptor endows these supramolecular fluorescent nanoparticles with excellent cancer imaging efficiency. We envisage that this novel class of supramolecular fluorescent nanoparticles will pave a new way to prepare highly fluorescent nanoparticles and can be further applied in the living systems. 5. Redox-responsive cationic supramolecular polymers as a gene vectorCurrently, almost all reported supramolecular vectors for gene therapy have been constructed through the host-guest complexation between high-molecular-weight polymers and low-molecular-weight cationic molecules. The high-molecular-weight polymer is the essential building block of the existing supramolecular gene vectors. Owing to facile depolymerization under exposure to concentration change, small molecule-based cationic supramolecular polymers for gene delivery have not yet been achieved. Therefore, the design and development of small molecule-based supramolecular gene vectors have become urgent and indispensable. In this chapter, we develop a new type of redox-responsive cationic supramolecular polymer via host-guest recognition between a β-cyclodextrin dimer and a ferrocene dimer, which showed redox-induced reversible polymerization and depolymerization upon alternating addition of hydrogen peroxide and glutathione. This small molecule-based supramolecular polymer exhibited effective DNA condensation ability and hydrogen peroxide-triggered DNA release behavior, which could be used in vitro as a promising nonviral vector for gene therapy. We believe that our work can further expand the field of application for small molecule-based supramolecular polymers. 6. Charge-tunable supramolecular dendritic polycations for gene deliveryGene transfection efficiency remarkably depends on structural parameters of cationic polymers including amino types, charge density and charge distribution. On one hand, the optimization of relevant structural parameters usually requires a large number of chemical syntheses or modifications, which makes the preparation of optimal cationic polymers tedious and further raises the cost of preparation. On the other hand, the structure-property relationship of cationic gene vectors cannot be predicted precisely, and thus the most optimized gene vectors are difficult to achieve by conventional covalent approach. To this end, a novel class of charge-tunable supramolecular dendritic polycations, which combine the multifunctionality of dendritic polymers with the dynamic-tunable nature of supramolecular polymers, has been successfully constructed through the host-guest interaction between two different cationic β-cyclodextrin derivatives as hosts and an adamantane-modified hyperbranched polyglycerol as a multivalent guest. In sharp contrast to the conventional covalent approach, this noncovalent preparation of supramolecular dendritic polycations provides a facile strategy to regulate the amino types, surface charge density, charge distribution and molecular functionality of cationic supramolecular polymers. As a result, the p DNA condensing ability and proton buffer capacity of supramolecular dendritic polycations can be readily optimized through tuning the molar ratio of these two cationic β-cyclodextrin derivatives, thereby leading to the enhancement of in vitro gene transfection efficiency. Therefore, this work provides a new strategy for the design and development of efficient gene vectors via noncovalent interactions.