Supramolecular self‐assembling peptide systems are attracting increasing interest in the field of cancer theranostics. Additionally, transformation of the immunologically cold tumor microenvironment ...into hot is of great importance for obtaining high antitumor responses for most immunotherapies. However, as far as it is known, there are nearly no studies on self‐assembling peptides reported to be able to convert cold to hot tumors. Herein, a self‐assembling peptide‐based cancer theranostic agent (named DBT‐2FFGYSA) is designed and synthesized, which can target tumor‐specific transmembrane Eph receptor A2 (EphA2) receptors selectively and make the receptors form large aggregates. Such aggregate formation promotes the cross‐phosphorylations among EphA2 receptors, leading to signal transduction of antitumor pathway. As a consequence, DBT‐2FFGYSA can not only visualize EphA2 receptors in a fluorescence turn‐on manner, but also specifically suppress the EphA2 receptor‐overexpressed cancer cell proliferation and tumor growth. What is more, DBT‐2FFGYSA also serves as an effective agent to convert immunologically cold tumors to hot by inducing the immunogenic cell death of EphA2 receptor‐overexpressed cancer cells and recruiting massive tumor‐infiltrating T cells. This study, thus, introduces a new category of agents capable of converting cold to hot tumors by pure supramolecular self‐assembly without any aid of known anticancer drugs.
A supramolecular self‐assembling peptide‐based molecule‐targeted anticancer agent (named DBT‐2FFGYSA) is designed and synthesized, which can precisely visualize transmembrane EphA2 receptors in a fluorescence turn‐on manner, selectively kill EphA2 receptor‐overexpressed cancer cells through making the receptors form large aggregates that activate antitumorigenic signaling, and effectively convert immunologically cold tumors to hot by recruiting tumor‐infiltrating T cells.
Abstract The article presents the authors’ approach to the development of a special adaptive tool with an autonomous energy source for tightening screws into threaded holes. The tool allows one to ...tighten and control threaded connections according to the assembly sequence of the device. A distinctive feature is its independence from the qualifications of the assembler, allowing to reduce the number of defects when assembling products.
Synthetic osteo‐promoting materials that are able to stimulate and accelerate bone formation without the addition of exogenous cells or growth factors represent a major opportunity for an aging world ...population. A co‐assembling system that integrates hyaluronic acid tyramine (HA‐Tyr), bioactive peptide amphiphiles (GHK‐Cu2+), and Laponite (Lap) to engineer hydrogels with physical, mechanical, and biomolecular signals that can be tuned to enhance bone regeneration is reported. The central design element of the multicomponent hydrogels is the integration of self‐assembly and enzyme‐mediated oxidative coupling to optimize structure and mechanical properties in combination with the incorporation of an osteo‐ and angio‐promoting segments to facilitate signaling. Spectroscopic techniques are used to confirm the interplay of orthogonal covalent and supramolecular interactions in multicomponent hydrogel formation. Furthermore, physico‐mechanical characterizations reveal that the multicomponent hydrogels exhibit improved compressive strength, stress relaxation profile, low swelling ratio, and retarded enzymatic degradation compared to the single component hydrogels. Applicability is validated in vitro using human mesenchymal stem cells and human umbilical vein endothelial cells, and in vivo using a rabbit maxillary sinus floor reconstruction model. Animals treated with the HA‐Tyr‐HA‐Tyr‐GHK‐Cu2+ hydrogels exhibit significantly enhanced bone formation relative to controls including the commercially available Bio‐Oss.
A multicomponent hydrogel platform that combines oxidative coupling with supramolecular co‐assembly to enable the tunability of physical, mechanical, and biological properties desirable in bone tissue regeneration is reported. The strategy permits the integration of the osteogenic properties of Laponite (Lap), the nanofibrous structure of peptide amphiphiles, the pro‐angiogenic properties of glycyl‐histidyl‐lysine (GHK) peptide, and the instant gelation of tyramine‐modified hyaluronic acid (HA‐Tyr).
Since the emergence of the concept of chemical topology, interlocked molecular assemblies have graduated from academic curiosities and poorly defined species to become synthetic realities. ...Coordination-directed synthesis provides powerful, diverse, and increasingly sophisticated protocols for accessing interlocked molecules. Originally, metal ions were employed solely as templates to gather and position building blocks in entwined or threaded arrangements. Recently, metal centers have increasingly featured within the backbones of the integral structural elements, which in turn use noncovalent interactions to self-assemble into intricate topologies. By outlining ingenious recent examples as well as seminal classic cases, this Review focuses on the role of metal–ligand paradigms in assembling molecular links. In addition, the ever-evolving approaches to efficient assembly, the structural features of the resulting architectures, and their prospects for the future are also presented.
In nanofibers composed of self‐assembling helical peptides, “capping” peptides can limit fiber growth and influence the character of immune responses raised by the materials. In article number ...2003310, Joel H. Collier and co‐workers design short peptides such that they self‐assemble into immunologically active helical nanofibers. The lengths of these fibers, tailorable by the incorporation of structure‐modifying peptides within the assemblies, influence the character of the immune responses they elicit. Image Credit: Chelsea Fries and Joel Collier.
Immunotherapy has received tremendous attention for tumor treatment, but the efficacy is greatly hindered by insufficient tumor‐infiltration of immune cells and immunosuppressive tumor ...microenvironment. The strategy that can efficiently activate cytotoxic T lymphocytes and inhibit negative immune regulators will greatly amplify immunotherapy outcome, which is however very rare. Herein, a new kind of semiconducting polymer (SP) nanoparticles is developed, featured with surface‐mimicking protein secondary structure (SPSS NPs) for self‐synergistic cancer immunotherapy by combining immunogenic cell death (ICD) and immune checkpoint blockade therapy. The SPs with excellent photodynamic property are synthesized by rational fluorination, which can massively induce ICD. Additionally, the peptide antagonists are introduced and self‐assembled into β‐sheet protein secondary structures on the photodynamic NP surface via preparation process optimization, which function as efficient lysosome‐targeting chimaeras (LYTACs) to mediate the degradation of programmed cell death ligand‐1 (PD‐L1) in lysosome. In vivo experiments demonstrate that SPSS NPs can not only elicit strong antitumor immunity to suppress both primary tumor and distant tumor, but also evoke long‐term immunological memory against tumor rechallenge. This work introduces a new kind of robust immunotherapy agents by combining well‐designed photosensitizer‐based ICD induction and protein secondary structures‐mediated LYTAC‐like multivalence PD‐L1 blockade, rendering great promise for synergistic immunotherapy.
A new kind of photodynamic semiconducting polymer nanoparticles with surface mimicking protein secondary structure (SPSS NPs) is developed to achieve self‐synergistic cancer immunotherapy by combining excellent immunogenic cell death and lysosome‐targeting chimaera‐like multivalent programmed cell death ligand‐1 blockade. SPSS NPs can not only effectively suppress both primary tumor and distant tumor, but also evoke long‐term immunological memory against tumor rechallenge.
Two-dimensional (2D) materials have attracted tremendous research interest since the breakthrough of graphene. Their unique optical, electronic, and mechanical properties hold great potential for ...harnessing them as key components in novel applications for electronics and optoelectronics. Their atomic thickness and exposed huge surface even make them highly designable and manipulable, leading to the extensive application potentials. What’s more, after acquiring the qualification for being the candidate for next-generation devices, the assembly of 2D materials monomers into mass or ordered structure is also of great importance, which will determine their ultimate industrialization. By designing the monomers and regulating their assembling behavior, the exploration of 2D materials toward the next-generation circuits can be spectacularly achieved. In this review, we will first overview the emerging 2D materials and then offer a clear guideline of varied physical and chemical strategies for tuning their properties. Furthermore, assembly strategies of 2D materials will also be included. Finally, challenges and outlooks in this promising field are featured on the basis of its current progress.
Self‐assembling peptide (SAP) hydrogels provide a fibrous microenvironment to cells while also giving users control of biochemical and mechanical cues. Previously, biochemical cues were introduced by ...physically mixing them with SAPs prior to hydrogel assembly, or by incorporating them into the SAP sequence during peptide synthesis, which limited flexibility and increased costs. To circumvent these limitations, we developed “Click SAPs,” a novel formulation that can be easily functionalized via click chemistry thiol‐ene reaction. Due to its high cytocompatibility, the thiol‐ene click reaction is currently used to crosslink and functionalize other types of polymeric hydrogels. In this study, we developed a click chemistry compatible SAP platform by addition of a modified lysine (lysine‐alloc) to the SAP sequence, enabling effective coupling of thiol‐containing molecules to the SAP hydrogel network. We demonstrate the flexibility of this approach by incorporating a fluorescent dye, a cellular adhesion peptide, and a matrix metalloproteinase‐sensitive biosensor using the thiol‐ene reaction in 3D Click SAPs. Using atomic force microscopy, we demonstrate that Click SAPs retain the ability to self‐assemble into fibers, similar to previous systems. Additionally, a range of physiologically relevant stiffnesses can be achieved by adjusting SAP concentration. Encapsulated cells maintain high viability in Click SAPs and can interact with adhesion peptides and a matrix metalloproteinase biosensor, demonstrating that incorporated molecules retain their biological activity. The Click SAP platform supports easier functionalization with a wider array of bioactive molecules and enables new investigations with temporal and spatial control of the cellular microenvironment.
Based on ab initio density functional calculations, we propose γ-P and δ-P as two additional stable structural phases of layered phosphorus besides the layered α-P (black) and β-P (blue) phosphorus ...allotropes. Monolayers of some of these allotropes have a wide band gap, whereas others, including γ-P, show a metal-insulator transition caused by in-layer strain or changing the number of layers. An unforeseen benefit is the possibility to connect different structural phases at no energy cost. This becomes particularly valuable in assembling heterostructures with well-defined metallic and semiconducting regions in one contiguous layer.
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