Ruijiao Dong

Functional supramolecular polymers for biomedical applications.

As a novel class of dynamic and non-covalent polymers, supramolecular polymers not only display specific structural and physicochemical properties, but also have the ability to undergo reversible changes of structure, shape, and function in response to diverse external stimuli, making them promising candidates for widespread applications ranging from academic research to industrial fields. By an elegant combination of dynamic/reversible structures with exceptional functions, functional supramolecular polymers are attracting increasing attention in various fields. In particular, functional supramolecular polymers offer several unique advantages, including inherent degradable polymer backbones, smart responsiveness to various biological stimuli, and the ease for the incorporation of multiple biofunctionalities (e.g., targeting and bioactivity), thereby showing great potential for a wide range of applications in the biomedical field. In this Review, the trends and representative achievements in the design and synthesis of supramolecular polymers with specific functions are summarized, as well as their wide-ranging biomedical applications such as drug delivery, gene transfection, protein delivery, bio-imaging and diagnosis, tissue engineering, and biomimetic chemistry. These achievements further inspire persistent efforts in an emerging interdisciplin-ary research area of supramolecular chemistry, polymer science, material science, biomedical engineering, and nanotechnology.

Supramolecular Dendritic Polymers: From Synthesis to Applications

CONSPECTUS: Supramolecular dendritic polymers (SDPs), which perfectly combine the advantages of dendritic polymers with those of supramolecular polymers, are a novel class of non-covalently bonded, highly branched macromolecules with three-dimensional globular topology. Because of their dynamic/reversible nature, unique topological structure, and exceptional physical/chemical properties (e.g., low viscosity, high solubility, and a large number of functional terminal groups), SDPs have attracted increasing attention in recent years in both academic and industrial fields. In particular, the reversibility of non-covalent interactions endows SDPs with the ability to undergo dynamic switching of structure, morphology, and function in response to various external stimuli, such as pH, temperature, light, stress, and redox agents, which further provides a flexible and robust platform for designing and developing smart supramolecular polymeric materials and functional supramolecular devices. The existing SDPs can be systematically classified into the following six major types according to their topological features: supramolecular dendrimers, supramolecular dendronized polymers, supramolecular hyperbranched polymers, supramolecular linear-dendritic block copolymers, supramolecular dendritic-dendritic block copolymers, and supramolecular dendritic multiarm copolymers. These different types of SDPs possess distinct morphologies, unique architectures, and specific functions. Benefiting from their versatile topological structures as well as stimuli-responsive properties, SDPs have displayed not only unique characteristics or advantages in supramolecular self-assembly behaviors (e.g., controllable morphologies, specific performance, and facile functionalization) but also great potential to be promising candidates in various fields. In this Account, we summarize the recent progress in the synthesis, functionalization, and self-assembly of SDPs as well as their potential applications in a wide range of fields. A variety of synthetic methods using non-covalent interactions have been established to prepare different types of SDPs based on varied mono- or multifunctionalized building blocks (e.g., monomer, dendron, dendrimer, and hyperbranched polymer) with homo- or heterocomplementary units. In addition, SDPs can be further endowed with excellent functionalities by employing different modification approaches involving terminal, focal-point, and backbone modification. Similar to conventional dendritic polymers, SDPs can self-assemble into diverse supramolecular structures such as micelles, vesicles, fibers, nanorings, tubes, and many hierarchical structures. Finally, we highlight some typical examples of recent applications of SDP-based systems in biomedical fields (e.g., controlled drug/gene/protein delivery, bioimaging, and biomimetic chemistry), nanotechnology (e.g., nanoreactors, catalysis, and molecular imprinting), and functional materials. The current research on SDPs is still at the very early stage, and much more work needs to be done. We anticipate that future studies of SDPs will focus on developing multifunctional, hierarchical supramolecular materials toward their practical applications by utilization of cooperative non-covalent interactions.

Photo-reversible supramolecular hyperbranched polymer based on host–guest interactions

A novel class of photo-responsive A2–B3 type supramolecular hyperbranched polymer with excellent optical properties can be polymerized and depolymerized reversibly by alternating UV/Vis light irradiation.

A supramolecular approach to the preparation of charge-tunable dendritic polycations for efficient gene delivery

A facile supramolecular approach for the preparation of charge-tunable dendritic polycations, by a combination of the multi-functionality of dendritic polymers with the dynamic-tunable ability of supramolecular polymers, has been developed. It provides a new strategy for designing and developing efficient gene vectors via noncovalent interactions.

Reversible photoisomerization of azobenzene-containing polymeric systems driven by visible light

A novel class of azobenzene-containing polymeric systems with reversible trans–cis photoisomerization behavior driven by visible light (ca. 450 nm) has been successfully prepared and this opens up a pathway for azobenzene-based systems in biomedical applications.

Synthesis and self-assembly of amphiphilic aptamer-functionalized hyperbranched multiarm copolymers for targeted cancer imaging.

A novel targeting cancer imaging platform based on aptamer-functionalized amphiphilic hyperbranched copolymer conjugates, which can self-assemble into nanoscopic micelles with a core-shell structure and a narrow size distribution, has been designed and synthesized. The size, morphology, fluorescence performance, and cytotoxicity of micelles were studied by dynamic light scattering, transmission electron microscopy, fluorescence spectroscopy, and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. The results indicate that these micelles have low cytotoxicity against MCF-7 cells and can be easily internalized by MCF-7 cells. In addition, they also exhibit enhanced cell uptake, excellent fluorescence properties, and smart targeting capability in vitro, indicating great potential to be promising carriers for bioimaging and cancer specific delivery.

Enhanced gene transfection efficiency of PDMAEMA by incorporating hydrophobic hyperbranched polymer cores: effect of degree of branching

Poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) is a well-known cationic polymer candidate for non-viral vectors for gene transfection. However, such an application has been greatly limited due to the cytotoxicity of the polymers. Herein, PDMAEMAs are grafted from hydrophobic hyperbranched PEHO cores (PEHO means poly(3-ethyl-3-(hydroxymethyl)-oxetane)), and the obtained hyperbranched multiarm copolymers of PEHO-g-PDMAEMAs show higher transfection efficiency than that of branched polyethylenimine (PEI) and PDMAEMA homopolymers, due to the improved cytotoxicity, DNA compaction, buffering ability and cellular uptake. In addition, to disclose the structure–property relationship, a series of PEHO-g-PDMAEMAs with different topological architectures are synthesized by changing the degrees of branching (DBs) of the PEHO cores and the lengths of the PDMAEMA arms. The ability of these vectors in DNA compaction, buffering ability, cytotoxicity and gene transfection efficiency is also investigated. It has been found the gene transfection efficiency of the vectors is dependent on the DB of the PEHO cores, but almost independent of the PDMAEMA arms in the experimental range.

Dual-responsive aggregation-induced emission-active supramolecular nanoparticles for gene delivery and bioimaging

Dual-responsive aggregation-induced emission-active supramolecular fluorescent nanoparticles are reported, which have the ability to undergo a unique morphological transition combining with a cooperative optical variation in response to pH and light stimuli. The dynamic supramolecular nanoparticles show excellent biocompatibility and effective plasmid DNA condensation capability, further achieving efficient in vitro gene delivery and bioimaging.

Synthesis of a Cationic Supramolecular Block Copolymer with Covalent and Noncovalent Polymer Blocks for Gene Delivery

The design and fabrication of safe and highly efficient nonviral vectors is the key scientific issue for the achievement of clinical gene therapy. Supramolecular cationic polymers have unique structures and specific functions compared to covalent cationic polymers, such as low cytotoxicity, excellent biodegradability, and smart environmental responsiveness, thereby showing great application prospect for gene therapy. However, supramolecular gene vectors are facile to be degraded under physiological conditions, leading to a significant reduction of gene transfection efficiency. In order to achieve highly efficient gene expression, it is necessary for supramolecular gene vectors being provided with appropriate biostability to overcome various cell obstacles. To this end, a novel cationic supramolecular block copolymer composed of a conventional polymer and a noncovalent polymer was constructed through robust β-cyclodextrin/ferrocene host-guest recognition. The resultant supramolecular block copolymer perfectly combines the advantages of both conventional polymers and supramolecular polymers ranging from structures to functions. This supramolecular copolymer not only has the ability to effectively condense pDNA for enhanced cell uptake, but also releases pDNA inside cancer cells triggered by H2O2, which can be utilized as a prospective nonviral delivery vehicle for gene delivery. The block polymer exhibited low cytotoxicity, good biostability, excellent biodegradability, and intelligent responsiveness, ascribing to the dynamic/reversible nature of noncovalent linkages. In vitro studies further illustrated that the supramolecular block polymer exhibited greatly improved gene transfection efficiency in cancer cells. This work offers an alternative platform for the exploitation of smart nonviral vehicles for specific cancer gene therapy in the future.