Journal of materials chemistry. B最新文献

For protein analysis, the current peptide-based probes rely almost on the specific recognition of the protein while neglecting the potential influence of the environment near the protein. Herein, we propose that to achieve high recognition of transmembrane protein integrin α_vβ₃, the interactions from the membrane substrate could be helpful. Moreover, to guarantee the additive effect of different interactions, the cis and trans isomers of peptide-based probes are distinguished. In detail, we synthesized the peptide-conjugated cis/trans isomers (cis-RTP and trans-RTP) by modifying the Arg-Gly-Asp (RGD)-targeting peptide and palmitic acid-conjugated Arg-Arg-Arg-Arg (Pal-RRRR) peptide to the two ends of the molecular scaffold-tetraphenylethene derivative. Due to the difference in spatial structure, isothermal titration calorimetry and simulation experiments demonstrated that cis-RTP can bind more stably to integrin α_vβ₃ than trans-RTP. As a result, cis-RTP has shown more excellent properties in inhibiting cell migration and killing cells by regulating actin and extracellular signal-regulated kinase. Unlike the existing probe design for protein, this study provides a concept of microenvironment-helpful recognition and a promising strategy of cis/trans isomers to modulate the interaction between proteins and probes.

Fused in sarcoma (FUS) is an intrinsically disordered RNA-binding protein that helps to regulate transcription and RNA transport while reversibly assembling into membraneless organelles (MLOs). Some mutations of FUS can promote irreversible aggregation, contributing to neurodegenerative diseases. We previously reported a multi-scale computational framework combining a series of molecular dynamics simulations (MD) followed by lattice Monte Carlo (MC) simulations to describe the tendency and dynamics of the assembly and disassembly of intrinsically disordered proteins (IDPs) using wild-type (WT)-FUS as an illustrative example. In this study, we utilized our computational model to simulate three FUS mutants widely experimented with glycine point mutation G156E, arginine point mutation R244C, and deletion of the C-terminal nuclear localization signal (ΔNLS). MD simulation results conveyed that G156E has improved sticker contact probability compared to WT-FUS, while R244C has slightly lower contact probability, which is also complemented by change of net interactions according to the molecular mechanics Poisson Boltzmann surface area (MMPBSA) method. The MC simulation results revealed that G156E has a higher aggregation propensity than the WT-FUS, while ΔNLS has more liquid-like assemblies. R244C demonstrated higher dynamics at the beginning, while over the evolution of MC simulations, it tends to aggregate compared to WT-FUS. In addition, the G156E mutant has more stable protein aggregates, lacking the rapid dynamics shown in all other scenarios. From the peak height of radial distribution functions (RDFs) of the assemblies, the phase separation propensity in ascending order is ΔNLS < FUS-WT < R244C < G156E. Moreover, interpreting the dynamic assembly propensity (DAP) parameter over time, the fluidity of the assemblies in ascending order is G156E < FUS-WT < R244C < ΔNLS. The results obtained from this study support that the computational model is able to predict the effect of mutation down to single amino acid substitution on the phase separation behavior of FUS. This efficient in silico method can be generalized to investigate the phase separation propensity of other IDPs and their mutants.

This study presents intercellular lipid-based Pickering emulsions (ILPEs) comprising a core of intercellular lipids (ILs) and an exterior solid layer of hectorite nanoplatelets (HNPs), formulated via an oil-in-water (O/W) Pickering emulsion technique to augment dermal penetration and moisture retention. Cationic surfactant-modified HNPs electrostatically interacted with stearic acid and ILs, forming robust, organized lamellar structures at the O/W interface and within the core. HNP integration into the IL matrix significantly elevated the interfacial modulus, enhancing emulsion stability. HNP- and SA-modified ILPEs demonstrated uniform distribution of a proxy drug across porcine epidermis to a depth of 20 μm, maintaining approximately 50% hydration after 72 h. These findings underscore the potential of ILPEs for cutaneous applications, offering superior stability, epidermal penetration, and improved stratum corneum hydration.

Rotator cuff tear repair poses significant challenges due to the complex gradient interface structure. In the face of disease-related disruptions in the tendon-bone interface (TBI), the strategy of constructing a biomimetic scaffold is a promising avenue. A novel 3D-printed rotator cuff scaffold loaded adipose stem cells (ADSCs), bone morphogenetic protein-2 (BMP-2), and collagen type I (COL I). The efficiency of the slow-release BMP-2 design depended on the dopamine-hyaluronic acid (HAD) and BMP-2 reaction. The cumulative release of BMP-2 was 44.97 ± 5.45% at 4 weeks. The 3D-printed bilayer scaffold, incorporating COL I and BMP-2, effectively promoted the differentiation of ADSCs into osteogenic, tenogenic, and chondrogenic lineages in vitro. The combination of 3D-printed bioactive scaffolds and ADSCs demonstrated a superior repair effect on rotator cuff injuries in vivo. Therefore, these findings indicates that the 3D-printed biomimetic scaffold loaded with ADSCs and BMP-2 holds potential as a promising graft for TBI healing.

Dynamic polymer materials can be obtained by introducing supramolecular interactions between the polymer chains. Here we report on the preparation and mechanical properties of poly(methyl acrylate) (PMA) and poly(n-butyl acrylate) (PBA) funcionalized with ureidopyrimidinone (UPy) in the side chains. In contrast to the traditional UPy with a methyl group, the selected UPy motif contained a branched alkyl side chain, which enhances solubility, compatibility with the polymer matrix and potentially prevents stacking of UPy dimers. Low molar mass PMA and PBA were synthesized via Cu(0)-mediated radical polymerization and allyl bonds were introduced with different degrees of functionalization by stoichiometrically controlled transesterification with allyl alcohol. The allyl esters served as functional handles for UPy attachment via UV-initiated radical thiol-ene coupling. The PMA-UPy materials displayed a more glassy appearance, in contrast to the rubbery PBA-UPy polymer networks, associated to its higher glass transition temperature. The mechanical properties of the resulting hydrogen bonded polymer networks were assessed by thermogravimetric analysis, differential scanning calorimetry, dynamic mechanical thermal analysis and tensile testing, followed by rheological analysis of the network dynamics. Furthermore, the effect of associative groups on the linear viscoelastic response is discussed based on a modified sticky Rouse model indicating the absence of significant aggregation or phase separation of the UPY units.

The unique microenvironment within living cells, characterized by high glutathione levels, reactive oxygen species concentrations, and active enzymes, facilitates the execution of chemical reactions. Recent advances in organic chemistry and chemical biology have leveraged living cells as reactors for chemical synthesis. This review summarizes recent reports on key intracellular in situ synthesis processes, including the synthesis of near-infrared fluorescent dyes, intracellular oxidative cross-linking, bioorthogonal reactions, and intracellular polymerization reactions. These methods have been applied to fluorescence imaging, tumor treatment, and the enhancement of biological functions. Finally, we discuss the challenges and opportunities in the field of in situ intracellular synthesis. We aim to guide the design of chemical molecules for in situ synthesis, improving the efficiency and control of artificial reactions in living cells, and ultimately achieving cell factory-like exogenous biological synthesis, biological function enhancement, and biomedical applications.

Macrophages play a crucial role in the process of wound healing. In order to effectively inhibit excessive inflammation and facilitate skin wound healing, it is necessary to transform overactive M1 macrophages in injured tissues into the M2 type. In this study, we have successfully generated bioinspired nanovesicles (referred to as M2BNVs) from M2 type macrophages. These nanovesicles not only possess physical and biological properties that closely resemble exosomes, but also offer a simpler preparation process and more abundant yield. Owing to their distinctive endogenous cargo, M2BNVs have the ability to re-educate M1 macrophages, shifting their phenotype towards the M2 type which is known to promote healing and possess anti-inflammatory properties. Consequently, M2BNVs effectively improve the prevailing pro-inflammatory microenvironment within the wound. Furthermore, M2BNVs also facilitate wound tissue regeneration and angiogenesis. Collectively, our findings demonstrate the potential of M2BNVs in promoting wound healing in mice.

The advent of lead-free perovskite materials with favorable toxicity profiles has made them candidates for in vivo and environmental applications. However, their tendency to leach A-site cations raises concerns about toxicity, catalytic efficiency, and slurry properties. The present study investigates the long-term leaching kinetics of BaTiO₃ powders over 31 days in aqueous solutions of varying pH levels. Using ICP-MS analysis and a numerical model based on the Unreacted Shrinking Core (USC) principle. The study extends the understanding of BaTiO₃ stability beyond previously reported timeframes. The findings highlight the material's long-term stability, with implications for biomedical and environmental applications.

Nasogastric tube (NGT) intubation is a common yet critical clinical procedure. However, complications arising from tube friction result in awful pain and morbidity. Here, we report a straightforward surface modification of slender NGT utilizing highly hydrated micelles that were composed of hyaluronic acid and Pluronic. The strong intermolecular hydrogen bonding facilitated the assembly of the micelles on NGT via a one-step dip coating process. The micelle coating conferred excellent hydrophilic, lubrication, anti-protein adhesive, and biocompatible properties. The in vivo efficacy of the micelle coating in alleviating catheterization irritation and mucosal injury was demonstrated using an NGT intubation model of rabbits. More importantly, compared to the paraffin oil coating (the current clinical means), the micelle coating possessed superior capability to reduce the inflammatory reaction caused by NGT intubation. The underlying mechanism was attributed to the suppression of the TLR4-IKBα-NF-κB inflammatory signaling pathway. This work provides a promising solution for developing lubricant medical coatings.

Chemotherapy-induced immunologic cell death is haunted by the non-specific distribution of chemotherapeutic drugs and insignificant immune activation effects, which render efforts to inhibit the distant metastasis of tumors frustrated. Given the pivotal role that lymph nodes play in tumor metastasis, it is of vital importance whether the drug delivery to tumor-draining lymph nodes (TDLNs) succeeds. In the current study, we developed a doxorubicin-albumin complex (DOX-HSA) solution with the specific ability to simultaneously target the primary tumor and the TDLNs. DOX-HSA could effectively activate and amplify the immunogenic cell death (ICD) effect in both the tumor tissues and the TDLNs, resulting in increased release of damage-associated molecular patterns (DAMPs), which further promoted phagocytosis and maturation of dendritic cells (DCs), stimulated activation of CD8⁺T cells, and then significantly enhanced the therapeutic effects of doxorubicin on orthotopic 4T1 tumor-bearing model mice. Therefore, the DOX-HSA solution demonstrated a more prominent ability to control cancer cells and curb metastasis, as well as improved security by reducing cardiotoxicity and myelosuppression toxicity of doxorubicin itself. This DOX-HSA strengthened the synergistic anti-tumor effects based on the ICD effect in combination with traditional chemotherapy, thus providing promising prospects for clinical application.