Materialomics integrates experiment, theory, and computation in a high‐throughput manner, and has changed the paradigm for the research and development of new functional materials. Recently, with the ...rapid development of high‐throughput characterization and machine‐learning technologies, the establishment of biomaterialomics that tackles complex physiological behaviors has become accessible. Breakthroughs in the clinical translation of nanoparticle‐based therapeutics and vaccines have been observed. Herein, recent advances in biomaterials, including polymers, lipid‐like materials, and peptides/proteins, discovered through high‐throughput screening or machine learning‐assisted methods, are summarized. The molecular design of structure‐diversified libraries; high‐throughput characterization, screening, and preparation; and, their applications in drug delivery and clinical translation are discussed in detail. Furthermore, the prospects and main challenges in future biomaterialomics and high‐throughput screening development are highlighted.
A systematic overview of the emerging field of intelligent biomaterialomics that integrates high‐throughput screening and data‐driven science to discover and design new biomaterials is presented. Methodologies for synthesizing biomaterials library, high‐throughput screening and characterization, and structure–activity relationships by data mining are summarized. Their biomedical applications, clinical translations, and challenges for future developments are highlighted.
Tumor complexity makes the development of highly sensitive tumor imaging probes an arduous task. Here, we construct a peptide‐based near‐infrared probe that is responsive to fibroblast activation ...protein‐α (FAP‐α), and specifically forms nanofibers on the surface of cancer‐associated fibroblasts (CAFs) in situ. The assembly/aggregation‐induced retention (AIR) effect results in enhanced accumulation and retention of the probe around the tumor, resulting in a 5.5‐fold signal enhancement in the tumor 48 h after administration compared to that of a control molecule that does not aggregate. The probe provides a prolonged detectable window of 48 h for tumor diagnosis. The selective assembly of the probe results in a signal intensity over four‐ and fivefold higher in tumor than in the liver and kidney, respectively. With enhanced tumor imaging capability, this probe can visualize small tumors around 2 mm in diameter.
Image of health: A peptide probe labeled with a near‐infrared dye has been developed that can be specifically tailored with a fibroblast activation protein‐α and then self‐assembled in situ into nanofibers on the surface of cancer‐associated fibroblasts. The selective assembly of the probe has resulted in tumor imaging with high sensitivity and specificity, with tumors as small as 2 mm in diameter visualized.
Precise and effective manipulation of protein functions still faces tremendous challenges. Herein we report a programmable peptide molecule, consisted of targeting and self‐assembly modules, that ...enables specific and highly efficient assembly governed by targeting receptor proteins. Upon binding to the cell membrane receptor, peptide conformation is somewhat stabilized along with decreased self‐assembly activation energy, promoting peptide‐protein complex oligomerization. We first design a GNNQQNY‐RGD peptide (G7‐RGD) to recognize integrin αVβ3 receptor for proof‐of‐concept study. In the presence of αVβ3 protein, the critical assembly concentration of free G7‐RGD decreases from 525 to 33 μM and the resultant G7‐RGD cluster drives integrin receptor oligomerization. Finally, a bispecific assembling peptide antiCD3‐G7‐RGD is rationally designed for cancer immunotherapy, which validates CD3 oligomerization and concomitant T cell activation, leading to T cell‐mediated cancer cell cytolysis.
The construction of a bispecific T‐cell engager (BiTE)‐like molecule is proposed. The peptide consists of dual CD3 and integrin αvβ3 targeting sequence, conjugated by a self‐assembling peptide. The molecule is designed to target the CD3 receptor on T cells and induce T cell‐mediated cytolysis against tumor cells overexpressing integrin αvβ3.
The fabrication of functional assemblies with defined structures through controllable molecular packing under physiological conditions is challenging. Here, modularly designed peptide‐cyanine ...conjugates that intracellularly self‐assembly into 1D columnar superstructures with controlled cyanine aggregation were designed, and they exhibit distinct imaging or photothermal properties. The peptide backbone is cleaved by caspase‐3/7 after entering the cells. Then the self‐assembled residue, with a double cyanine substitution (Pr‐2Cy), forms a P helical column in which H‐aggregated cyanine dyes show 3.4‐fold photothermal conversion efficiency compared to free ones. The self‐assembled residue with a single cyanine substitution (Pr‐1Cy) forms a loose column, in which cyanine dyes with undefined structure have a fluorescence quantum yield of up to 9.5 % (emission at 819 nm in H2O). This work provides a simple way to modify in vivo self‐assembled peptides with functional molecules for achieving desired bio‐applications.
The design of peptide‐cyanine conjugates that intracellularly self‐assemble into a one‐dimensional column with controlled cyanine aggregation exhibit distinct imaging or photothermal properties. Through rational molecular design, the assembly behavior of cyanine dyes is precisely regulated in biological systems, resulting in two kinds of assemblies with different properties. The relationship between structure and function has been studied in detail.
Under investigation in this work is a generalized
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-dimensional Boussinesq equation. By employing the Bell’s polynomials, bilinear formalism of this generalized
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-dimensional ...Boussinesq equation is succinctly derived. With the aid of the obtained bilinear formalism, general high-order breather solutions are constructed by using the Hirota’s bilinear method combined with the perturbation expansion. The breathers only periodically propagate along the
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-dimensional Boussinesq equation would be succinctly constructed. These smooth rational solutions are high-order lumps and mixed solutions comprising a line rogue wave and lumps. These results exhibit the dynamical behavior of the generalized
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The maintenance of tissue homeostasis is critically dependent on the function of tissue-resident immune cells and the differentiation capacity of tissue-resident stem cells (SCs). How immune cells ...influence the function of SCs is largely unknown. Regulatory T cells (Tregs) in skin preferentially localize to hair follicles (HFs), which house a major subset of skin SCs (HFSCs). Here, we mechanistically dissect the role of Tregs in HF and HFSC biology. Lineage-specific cell depletion revealed that Tregs promote HF regeneration by augmenting HFSC proliferation and differentiation. Transcriptional and phenotypic profiling of Tregs and HFSCs revealed that skin-resident Tregs preferentially express high levels of the Notch ligand family member, Jagged 1 (Jag1). Expression of Jag1 on Tregs facilitated HFSC function and efficient HF regeneration. Taken together, our work demonstrates that Tregs in skin play a major role in HF biology by promoting the function of HFSCs.
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•Treg activation in skin closely correlates with the HF cycle•Tregs localize to HFSCs and play a major role in HF regeneration•Tregs facilitate HFSC proliferation and differentiation to initiate HF cycling•Treg expression of Jagged 1 is required for efficient hair regeneration
Localized regulatory T cells (Tregs) regulate the hair follicle cycle by driving Notch-dependent stem cell proliferation and differentiation.
Achieving the activation of drugs within cellular systems may provide targeted therapies. Here we construct a tumour-selective cascade activatable self-detained system (TCASS) and incorporate imaging ...probes and therapeutics. We show in different mouse models that the TCASS system accumulates in solid tumours. The molecules show enhanced accumulation in tumour regions via the effect of recognition induced self-assembly. Analysis of the molecular penetration in tumour tissue shows that in vivo self-assembly increases the penetration capability compared to typical soft or hard nanomaterials. Importantly, the in vivo self-assembled molecules exhibit a comparable clearance pathway to that of small molecules, which are excreted from organs of the reticuloendothelial system (liver and kidney), while are relatively slowly eliminated from tumour tissues. Finally, this system, combined with the NIR probe, shows high specificity and sensitivity for detecting bladder cancer in isolated intact patient bladders.
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