Polyphenols, due to their high biocompatibility and wide occurrence in nature, have attracted increasing attention in the engineering of functional materials ranging from films, particles, to bulk hydrogels. Colloidal particles, such as nanogels, hollow capsules, mesoporous particles and core-shell structures, have been fabricated from polyphenols or their derivatives with a series of polymeric or biomolecular compounds through various covalent and non-covalent interactions. These particles can be designed with specific properties or functionalities, including multi-responsiveness, radical scavenging capabilities, and targeting abilities. Moreover, a range of cargos (e.g., imaging agents, anticancer drugs, therapeutic peptides or proteins, and nucleic acid fragments) can be incorporated into these particles. These cargo-loaded carriers have shown their advantages in the diagnosis and treatment of diseases, especially of cancer. In this review, we summarize the assembly of polyphenol-based particles, including polydopamine (PDA) particles, metal-phenolic network (MPN)-based particles, and polymer-phenol particles, and their potential biomedical applications in various diagnostic and therapeutic applications.

Injectable and sprayable hydrogels have attracted considerable attention for application in the biomedical field owing to their high moldability and efficiency in encapsulating therapeutics and cells. Herein, we report the spontaneous assembly of injectable and sprayable hydrogels via a one-step mixing of solutions of tannic acid (TA) and O-carboxymethyl chitosan (CMCS) without an external stimulus. The presence of 1,4-benzenediboronic acid (BDBA) improves the mechanical properties and reduces the gelation time of the resulting hydrogels. The hydrogels assemble via hydrogen bonds between TA and CMCS as well as via dynamic boronate ester bonds between TA and BDBA, as confirmed by Fourier transform infrared spectroscopy. Balancing the interactions between the three components (CMCS/TA/BDBA) is essential for the construction of the hydrogels. The moduli of the CMCS–TA–BDBA hydrogels initially increase as the amount of BDBA increases and decrease after reaching a maximum value at a BDBA-to-TA molar ratio of 3:1. The CMCS–TA–BDBA hydrogels with interconnected porous morphologies display rapid gelation (∼10 s), biocompatibility, self-healing, injectable, and sprayable abilities. In addition, the hydrogels can be used for hemostasis. The extent of bleeding in mouse livers treated with the hydrogels could be reduced extensively from 240 (nontreated mouse livers) to 55 mg (77% reduction). The reported hydrogels coupled with the combination of functionality and biological activity make them promising hemostatic materials for biomedical applications.

Fast and facile coating strategies play a key role in surface engineering and functionalization of materials for various applications. Herein, we report a rapid and eco-friendly hair dyeing process for natural gray hair via the formation of metal–phenolic networks (MPNs). MPNs composed of gallic acid display high performance, and the coloration is tunable by varying the metal ion types. MPN-based hair dyeing is tolerant to repeated washing (at least 50 times) with detergent solution without color fading and can be discolored in acidic solution (pH < 2). The mechanism of self-assembled MPNs for hair dyeing is investigated by Raman and UV–vis absorption spectroscopy. Cell studies in vitro and skin toxicity tests in vivo demonstrate the advantages (i.e., biocompatibility and hair regrowth) of MPNs for hair dyeing compared to p-phenylenediamine. The reported strategy for hair dyeing avoids the use of toxic substances present in common hair dyes and has negligible damage to the hair structures and tensile strength.

Four cyclo(l-Lys-l-Glu) derivatives (3-6) were synthesized from the coupling reaction of protecting l-lysine with l-glutamic acid followed by the cyclization, deprotection, and protection reactions. They can efficiently gelate a wide variety of organic solvents or water. Interestingly, a spontaneous chemical reaction proceeded in the organogel obtained from 3 in acetone exhibiting not only visual color alteration but also increasing mechanical strength with the progress of time due to the formation of Schiff base. Moreover, 6 bearing a carboxylic acid and Fmoc group displayed a robust hydrogelation capability in PBS solution. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) revealed the characteristic gelation morphologies of 3D fibrous network structures in the resulting organo- and hydrogels. FT-IR and fluorescence analyses indicated that the hydrogen bonding and π-π stacking play as major driving forces for the self-assembly of these cyclic dipeptides as low-molecular-weight gelators. X-ray diffraction (XRD) measurements and computer modeling provided information on the molecular packing model in the hydrogelation state of 6. A spontaneous chemical reaction proceeded in the organogel obtained from 3 in acetone exhibiting visual color alteration and increasing mechanical strength. 6 bearing an optimized balance of hydrophilicity to lipophilicity gave rise to a hydrogel in PBS with MGC at 1 mg/mL.

Conspectus Supramolecular assembly is commonly driven by noncovalent interactions (e.g., hydrogen bonding, electrostatic, hydrophobic, and aromatic interactions) and plays a predominant role in multidisciplinary research areas ranging from materials design to molecular biology. Understanding these noncovalent interactions at the molecular level is important for studying and designing supramolecular assemblies in chemical and biological systems. Cation−π interactions, initially found through their influence on protein structure, are generally formed between electron-rich π systems and cations (mainly alkali, alkaline-earth metals, and ammonium). Cation−π interactions play an essential role in many biological systems and processes, such as potassium channels, nicotinic acetylcholine receptors, biomolecular recognition and assembly, and the stabilization and function of biomacromolecular structures. Early fundamental studies on cation−π interactions primarily focused on computational calculations, protein crystal structures, and gas- and solid-phase experiments. With the more recent development of spectroscopic and nanomechanical techniques, cation−π interactions can be characterized directly in aqueous media, offering opportunities for the rational manipulation and incorporation of cation−π interactions into the design of supramolecular assemblies. In 2012, we reported the essential role of cation−π interactions in the strong underwater adhesion of Asian green mussel foot proteins deficient in l-3,4-dihydroxyphenylalanine (DOPA) via direct molecular force measurements. In another study in 2013, we reported the experimental quantification and nanomechanics of cation−π interactions of various cations and π electron systems in aqueous solutions using a surface forces apparatus (SFA). Over the past decade, much progress has been achieved in probing cation−π interactions in aqueous solutions, their impact on the underwater adhesion and cohesion of different soft materials, and the fabrication of functional materials driven by cation−π interactions, including surface coatings, complex coacervates, and hydrogels. These studies have demonstrated cation−π interactions as an important driving force for engineering functional materials. Nevertheless, compared to other noncovalent interactions, cation−π interactions are relatively less investigated and underappreciated in governing the structure and function of supramolecular assemblies. Therefore, it is imperative to provide a detailed overview of recent advances in understanding of cation−π interactions for supramolecular assembly, and how these interactions can be used to direct supramolecular assembly for various applications (e.g., underwater adhesion). In this Account, we present very recent advances in probing and applying cation−π interactions for mussel-inspired supramolecular assemblies as well as their structural and functional characteristics. Particular attention is paid to experimental characterization techniques for quantifying cation−π interactions in aqueous s...