Nature endows life with a wide variety of sophisticated, synergistic, and highly functional protein assemblies. Following Nature's inspiration to assemble protein building blocks into exquisite nanostructures is emerging as a fascinating research field. Dictating protein assembly to obtain highly ordered nanostructures and sophisticated functions not only provides a powerful tool to understand the natural protein assembly process but also offers access to advanced biomaterials. Over the past couple of decades, the field of protein assembly has undergone unexpected and rapid developments, and various innovative strategies have been proposed. This Review outlines recent advances in the field of protein assembly and summarizes several strategies, including biotechnological strategies, chemical strategies, and combinations of these approaches, for manipulating proteins to self-assemble into desired nanostructures. The emergent applications of protein assemblies as versatile platforms to design a wide variety of attractive functional materials with improved performances have also been discussed. The goal of this Review is to highlight the importance of this highly interdisciplinary field and to promote its growth in a diverse variety of research fields ranging from nanoscience and material science to synthetic biology.
The macrocyclic molecular container cucurbit [7]uril (CB[7]), the most water-soluble homologue in the cucurbit[n]uril family (n = 5-8, 10, 14), has been evaluated for its in vivo toxicity profile, including its developmental toxicity such as its effect on hatching, growth and survival, as well as its potential organ-specific toxicities such as cardiotoxicity, hepatotoxicity, and locomotion and behavioral toxicity, using zebrafish models. The results revealed that CB[7] has measureable cardiotoxicity and locomotion and behavioral toxicity at concentrations of ~500 µM or higher, and negligible developmental and hepatotoxicity at concentrations up to 750 µM, although extended exposure to CB[7] at the 500-750 µM concentration range induced the mortality of tested fish. These results demonstrate for the first time with live in vivo animal models that
Vascular disease remains the leading cause of death and disability, the etiology of which often involves atherosclerosis. The current treatment of atherosclerosis by pharmacotherapy has limited therapeutic efficacy. Here we report a biomimetic drug delivery system derived from macrophage membrane coated ROS-responsive nanoparticles (NPs). The macrophage membrane not only avoids the clearance of NPs from the reticuloendothelial system, but also leads NPs to the inflammatory tissues, where the ROS-responsiveness of NPs enables specific payload release. Moreover, the macrophage membrane sequesters proinflammatory cytokines to suppress local inflammation. The synergistic effects of pharmacotherapy and inflammatory cytokines sequestration from such a biomimetic drug delivery system lead to improved therapeutic efficacy in atherosclerosis. Comparison to macrophage internalized with ROS-responsive NPs, as a live-cell based drug delivery system for treatment of atherosclerosis, suggests that cell membrane coated drug delivery approach is likely more suitable for dealing with an inflammatory disease than the live-cell approach.
Proteins are an endless source of inspiration. By carefully tuning the amino‐acid sequence of proteins, nature made them evolve from primary to quaternary structures, a property specific to protein oligomers and often crucial to accomplish their function. On the other hand, the synthetic macrocycles cucurbiturils (CBs) have shown outstanding recognition properties in water, and a growing number of (host)n:(guest)n supramolecular polymers involving CBs have been reported. However, the burgeoning field of discrete (n:n) host:guest oligomers has just started to attract attention. While 2:2 complexes are the major oligomers, 3:3 and up to 6:6 oligomers have been described, some associated with emerging applications, specific to the (n:n) arrangements. Design rules to target (n:n) host:guest oligomers are proposed toward new advanced host:guest systems.
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