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Under the unmet need of efficient tumor‐targeting drugs for oncology, a recombinant version of the plant toxin ricin (the modular protein T22‐mRTA‐H6) is engineered to self‐assemble as protein‐only, CXCR4‐targeted nanoparticles. The soluble version of the construct self‐organizes as regular 11 nm planar entities that are highly cytotoxic in cultured CXCR4+ cancer cells upon short time exposure, with a determined IC50 in the nanomolar order of magnitude. The chemical inhibition of CXCR4 binding sites in exposed cells results in a dramatic reduction of the cytotoxic potency, proving the receptor‐dependent mechanism of cytotoxicity. The insoluble version of T22‐mRTA‐H6 is, contrarily, moderately active, indicating that free, nanostructured protein is the optimal drug form. In animal models of acute myeloid leukemia, T22‐mRTA‐H6 nanoparticles show an impressive and highly selective therapeutic effect, dramatically reducing the leukemia cells affectation of clinically relevant organs. Functionalized T22‐mRTA‐H6 nanoparticles are then promising prototypes of chemically homogeneous, highly potent antitumor nanostructured toxins for precise oncotherapies based on self‐mediated intracellular drug delivery.  相似文献   

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An analysis of the accumulated knowledge on virus-based nanoparticles (VNPs) consisting of virus protein capsids and inorganic cargo, such as nanoparticles (NPs), nanowires, and thin layers, is presented. Virus capsids (VCs) can serve either as templates or nanoreactors when inorganic materials are formed outside or inside VCs. The third possibility is when inorganic NPs nucleate the formation of VCs. The structural and mechanistic studies of VNP formation are paving the way to a better understating of virus structure and behavior, and these facilitate promising applications of VNPs in biomedical and materials research.  相似文献   

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The development of extracellular matrix mimetics that imitate niche stem cell microenvironments and support cell growth for technological applications is intensely pursued. Specifically, mimetics are sought that can enact control over the self‐renewal and directed differentiation of human pluripotent stem cells (hPSCs) for clinical use. Despite considerable progress in the field, a major impediment to the clinical translation of hPSCs is the difficulty and high cost of large‐scale cell production under xeno‐free culture conditions using current matrices. Here, a bioactive, recombinant, protein‐based polymer, termed ZTFn, is presented that closely mimics human plasma fibronectin and serves as an economical, xeno‐free, biodegradable, and functionally adaptable cell substrate. The ZTFn substrate supports with high performance the propagation and long‐term self‐renewal of human embryonic stem cells while preserving their pluripotency. The ZTFn polymer can, therefore, be proposed as an efficient and affordable replacement for fibronectin in clinical grade cell culturing. Further, it can be postulated that the ZT polymer has significant engineering potential for further orthogonal functionalization in complex cell applications.  相似文献   

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Proteinaceous materials based on the amyloid core structure have recently been discovered at the origin of biological functionality in a remarkably diverse set of roles, and attention is increasingly turning towards such structures as the basis of artificial self‐assembling materials. These roles contrast markedly with the original picture of amyloid fibrils as inherently pathological structures. Here we outline the salient features of this class of functional materials, both in the context of the functional roles that have been revealed for amyloid fibrils in nature, as well as in relation to their potential as artificial materials. We discuss how amyloid materials exemplify the emergence of function from protein self‐assembly at multiple length scales. We focus on the connections between mesoscale structure and material function, and demonstrate how the natural examples of functional amyloids illuminate the potential applications for future artificial protein based materials.  相似文献   

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Methods for combining multiple functions into well-defined nanomaterials are still lacking, despite their need in nanomedicine and within the broader field of nanotechnology. Here several strategies for controlling the amount and the ratio of combinations of labeled DNA on 13-nm gold nanoparticles using self-assembly of thiolated DNA and/or DNA-directed assembly are explored. It is found that the self-assembly of mixtures of fluorescently labeled DNA can lead to a higher amount of labeled DNA per particle; however, the ratio of fluorophores on the nanoparticles differs greatly from that in the self-assembly solution. In contrast, when fluorescently labeled DNA are hybridized to DNA-modified gold nanoparticles, the fluorophore ratio on the nanoparticles is much closer to their ratio in solution. The use of bifunctional DNA-doublers in self-assembly and DNA-directed assembly is also explored to increase the complexity of these materials and control their composition. Finally, tuning the distance between the labels from 2.9 to 5.4 nm was achieved using different hybridized DNA clamp complexes. Fluorescent results suggest that assembling these clamps on nanoparticle surfaces may be possible, although the resulting label spacing could not be quantified.  相似文献   

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Nanoparticles tend to aggregate once integrated into soft matter and consequently, self‐assembling nanoparticles into large‐scale, regular, well‐defined, and ultimately chiral patterns remains an ongoing challenge toward the design and realization of organized superstructures of nanoparticles. The patterns of nanoparticles that are reported in liquid crystals so far are all static, and this lack of responsiveness extends to assemblies of nanoparticles formed in topological singularities and other localized structures of anisotropic matter. Here, it is shown that gold nanoparticles form spiral superstructures in polygonal fields of cholesteric liquid crystals. Moreover, when the cholesteric liquid crystals incorporate molecular photoswitches in their composition, the pitch of the nanoparticulate spirals follows the light‐induced reorganization of the cholesteric liquid crystals. These experimental findings indicate that chiral liquid crystals can be used as chiral and dynamic templates for soft photonic nanomaterials. Controlling the geometry of these spirals of nanoparticles will ultimately allow modulating the plasmonic signature of hybrid and chiral systems.  相似文献   

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