The Royal Society of Chemistry最新文献

Ferroptosis is a form of iron-dependent cell death pattern distinct from apoptosis, providing new targets for cancer therapeutics. By regulating cellular iron metabolism, destroying redox imbalance defenses and/or promoting lipid peroxidation, ferroptotic therapy induces ferroptosis of tumor cells, thereby circumventing resistance issues associated with the overwhelmingly used apoptosis-based treatments. Importantly, there are myriad interactions between ferroptotic tumor cells and the tumor microenvironment (TME), especially for solid tumors, which would greatly impact therapeutic outcomes. Therefore, it is crucial to simultaneously manipulate tumor cell ferroptosis and TME modulation through rational drug combinations, necessitating the development of relevant nanoplatforms. This review begins by elaborating on the interactions between ferroptotic tumor cells and the TME: on one hand, ferroptosis of tumor cells may activate or suppress immune cells in the TME through diverse mechanisms; on the other hand, the TME (considering its special components and properties) may alter the susceptibility of tumor cells to ferroptotic therapy. Next, we focus on recently reported nanoplatforms capable of simultaneously activating tumor cell ferroptosis and remodeling the TME, providing a systematic analysis of nanoplatform design/construction, drug combination strategies, as well as their advantages and disadvantages. Given the importance of the interactions between tumor cell ferroptosis and the TME, this work aims to offer valuable insights for the exploration of novel targets for reinforced anti-tumor treatment and the design of relevant nanoplatforms.

Planar, carbon-electrode-based perovskite solar cells (C-PSCs) without a hole transport layer (HTL) are highly attractive due to their simple fabrication, low cost, and scalability. However, their performance is often limited by inefficient physical and electrical contact at the perovskite/carbon interface, which impedes hole extraction and promotes charge recombination. This study introduces a pre-engineered, multifunctional interlayer for HTL-free C-PSCs utilizing tetrabutylammonium ion (TBA⁺)-intercalated black phosphorus quantum dots (BPQDs). The TBA⁺ intercalation during synthesis pre-engineers the BPQDs with enhanced conductivity, a raised valence band maximum (-5.27 eV), and defect-passivation capabilities. This creates a favorable cascade energy-level alignment between the perovskite absorber (-5.5 eV) and the carbon electrode (-5.0 eV), thereby facilitating efficient hole extraction. The BPQDs interlayer also ensures seamless perovskite/carbon contact, promoting interfacial charge transfer. Additionally, TBA⁺ ions released from BPQDs effectively passivate defects on the perovskite surface, suppressing nonradiative recombination. Consequently, the optimized devices achieve a power conversion efficiency (PCE) of 17.08%, which is 24.1% and 11.9% higher than that of control devices without an interlayer (13.76%) and with a pristine BPQDs interlayer (15.26%), respectively. Furthermore, the encapsulated devices demonstrate improved operational stability, retaining 89.1% of their initial PCE after 360 hours under 1-sun illumination at 85 °C and 85% relative humidity.

The morphology and chain orientation of conjugated polymer films strongly influence their charge transport properties. In this study, we investigate the solution crystallization behavior of semiconducting polymers in nanoconfinement generated using 1,3,5-trichlorobenzene (sym-TCB), a solvent additive that crystallizes at room-temperature. Solutions of a diketopyrrolopyrrole-bithiophene (pDPPBT) copolymer, poly(3-hexylthiophene) (P3HT), and other polymers were prepared in chloroform with varying concentrations of sym-TCB. Upon film casting, sym-TCB crystals directed the growth of polymer domains, resulting in spherulitic morphologies replicated from the solvent crystals. pDPPBT films exhibited predominantly edge-on chain orientation at the dielectric interface, whereas P3HT showed bimodal orientation: face-on alignment near the top film surface via epitaxial crystallization and edge-on alignment at the bottom interface. This crystallization behavior was also observed in other conjugated polymer systems. Notably, pDPPBT films with conductive domains templating the solvent crystals significantly enhanced field-effect mobility (∼5.60 cm² V^-1 s^-1), outperforming control films with randomly aligned fibrillar domains (1.60-2.40 cm² V^-1 s^-1). These findings demonstrate that solvent crystal-induced nanoconfinement enables precise control over multiscale polymer ordering, offering an effective strategy to enhance charge transport in organic thin-film transistors.

This work describes an electrochemical biosensor using iron-doped copper nitride (Cu₃N-Fe) nanostructures for the rapid detection of hydrogen peroxide (H₂O₂), a key metabolic biomarker released by cancer cells. The sensor, prepared by drop-casting the nanocomposite onto a glassy carbon electrode, shows high electrocatalytic activity towards H₂O₂ oxidation, with a wide linear range from 0.01 mM to 1 M and a detection limit of 9.8 µM. The sensor successfully differentiated multiple cancer cell lines from non-cancerous controls and was clinically validated using 28 cancer patient tissue samples, distinguishing cancerous from adjacent normal tissues with approximately 90% accuracy. A strong positive correlation was established between the response of the sensor and the expression levels of formyl peptide receptor-1 in the cancer tissues, which validates the sensing mechanism. This work shows the potential of Cu₃N-Fe as a material for developing cost-effective, point-of-care diagnostic tools for rapid, qualitative cancer screening.

Tissue engineering is an emerging and integrated field for the repair of defective tissues, which benefits from the interdisciplinary development of biomaterial and engineering techniques. Electrospinning is a promising technique used in tissue engineering to fabricate fiber-based biomaterials that could mimic the extracellular matrix even at the nanometer level, but there has been no review to identify the trends and systematically summarize the application strategies of electrospinning in tissue engineering. This review initially used bibliometric analysis to investigate the trends of electrospinning in tissue engineering from the beginning of this century by evaluating distinctive aspects including publication years, countries, institutions, and keywords. Then, this review presents the multi-hierarchical strategies used in electrospinning to fabricate functional scaffolds for tissue engineering, including biochemical modification, biophysical modification and cell incorporation. Moreover, the hybrid combinations of electrospinning with other biofabrication techniques to fabricate composite scaffolds are summarized including textile, 3D printing, hydrogel, lyophilization and gas foaming, thus finely simulating the bionic 3D microenvironment or the complex/interfacial tissue structures. Finally, this review discusses the research prospects and ongoing challenges, aiming to promote further development and clinical transformation.

Given the potential of polyphenols to mitigate neurodegenerative diseases (NDDs), this meta-analysis investigated whether clinical evidence supports the use of polyphenols for neuroprotection and as nutritional strategies in NDDs. We analyzed different polyphenol types across seven NDDs, 13 studies involving 849 participants were included. Prespecified outcomes comprised global cognition (Mini-Mental State Examination, MMSE), domain-specific cognition (Alzheimer's Disease Cooperative Study-Cognitive Subscale, ADCS-Cog), activities of daily living (Alzheimer's Disease Cooperative Study-Activities of Daily Living, ADCS-ADL), neuropsychiatric symptoms (Neuropsychiatric Inventory, NPI), and selected biomarkers (plasma amyloid-β40 and brain-derived neurotrophic factor, BDNF). Reporting followed PRISMA 2020 guidelines, methods conformed to the Cochrane Handbook, and certainty of evidence was assessed using GRADE. Overall, polyphenol supplementation was associated with improved global cognition (pooled MD in MMSE = 2.06; 95% CI 0.62-3.49). In subgroup analyses, flavonoids were associated with a modest but significant improvement in MMSE scores, whereas stilbenes produced a significant benefit in daily functioning (ADCS-ADL) without clear gains in MMSE or ADCS-Cog and no consistent effects on NPI. Anthocyanidins, phenolic acids, and lignans did not significantly affect cognitive outcomes (MMSE or ADCS-Cog), and polyphenol subclasses did not yield robust or consistent changes in NPI or biomarker endpoints (Aβ40 and BDNF). Specific polyphenol subclasses therefore appear to confer selective cognitive and functional benefits, with stilbenes primarily supporting functional outcomes and flavonoids potentially enhancing global cognition.

Dietary advanced glycation end products (AGEs), formed during thermal food processing, are associated with metabolic disorders. This study investigated the efficacy of rutin in alleviating AGEs-induced insulin resistance (IR) in a mouse model. Male C57BL/6 mice were fed a high-AGEs diet for 12 weeks to induce IR, followed by 8 weeks of rutin intervention (100 mg per kg body weight per day). Rutin supplementation markedly ameliorated IR, as indicated by reduced hyperglycemia and dyslipidemia, a reduced homeostasis model assessment of insulin resistance (HOMA-IR) index, an elevated insulin sensitivity (HOMA-IS) index, and upregulation of insulin receptor substrates IRS-1 and IRS-2. Metagenomic analysis demonstrated that rutin intervention restored gut microbial richness and diversity and induced structural shifts in the microbiota composition. Specifically, rutin enriched beneficial genera, including Akkermansia, Bifidobacterium, Faecalibacterium, Lactobacillus, and Coriobacteriales, while reducing populations of IR-associated taxa such as Erysipelotrichaceae, Coprobacillus, Enterococcus, Adlercreutzia, and Allobaculum. Concurrently, rutin increased fecal concentrations of short-chain fatty acids (SCFAs), notably acetic acid and propionic acid. Spearman's correlation analysis confirmed negative associations between rutin-modulated microbiota and IR indicators. These results demonstrate that rutin mitigates AGEs-induced IR by reshaping the gut microbiome and promoting beneficial microbial metabolites.

Coenzyme Q10 (CoQ₁₀) is a mitochondrial electron carrier and antioxidant widely used in cardiovascular, neurodegenerative, and metabolic disorders; however, its oral efficacy is severely limited by extremely low aqueous solubility, high crystallinity, and poor bioavailability. Although several lipid-based and nanoformulations have been explored, many suffer from limited stability, incomplete suppression of crystallinity, or modest pharmacokinetic improvement. The objective of this study was to develop a stable, scalable liposomal CoQ₁₀ formulation and to evaluate its physicochemical properties and human oral bioavailability. Metazomal CoQ₁₀ (MCQ) was developed using Metazome technology, in which CoQ₁₀ was incorporated into phospholipid bilayers reinforced with gum arabic nanospheres and converted into a dry, reconstitutable liposomal powder by spray drying. MCQ formed nanosized (∼185 nm), spherical vesicles with high encapsulation efficiency (88.6 ± 2.3%), favorable loading capacity (14.2 ± 0.8%), strong electrostatic stability (zeta potential -41.16 mV), and amorphous molecular dispersion of CoQ₁₀. The formulation retained >90% of CoQ₁₀ after 180 days at room temperature. In a randomized, open-label, crossover study in healthy volunteers, MCQ demonstrated significantly improved pharmacokinetics compared with conventional CoQ₁₀ (CCQ), including a 4.3-fold increase in AUC_0-t, a 3.6-fold increase in C_max, prolonged T_max, extended half-life, and a lower elimination rate constant (p < 0.01). The integrated Metazome-based architecture represents a key innovation by combining amorphization, nanoscale liposomal delivery, and structural stabilization, resulting in superior stability and markedly enhanced human bioavailability. MCQ therefore offers strong potential for nutraceutical and therapeutic applications requiring improved and sustained CoQ₁₀ exposure.

Caffeic acid (CA) has been found to have the potential to inhibit the growth of human colorectal cancer HT-29 cells in vitro. However, the effects of CA administration on colorectal cancer growth and immunity in vivo remain unclear. To unravel the mystery of CA administration on cancer cell growth, serum antibody titers, lymphoid lineage cells in the peripheral blood, and the M1/M2 immune balance in BALB/c nude mice subcutaneously loaded with human colorectal cancer HT-29 cells for 35 days were examined in the experiment. The experimental mice were respectively given low (6 mg CA per kg AIN-93M feed), medium (30 mg CA per kg AIN-93M feed), and high (60 mg CA per kg AIN-93M feed) doses for 35 days. The results showed that CA administration tended to decrease the cancer cell volume and serum IgG and IgM levels compared to those in the dietary control (DC) group. CA administration slightly increased the proportion of CD3⁺ T and CD49⁺ natural killer cells, but decreased CD19⁺ B cells in the peripheral blood compared to those in the DC group, causing the immune cell distribution to be closer to the vehicle control (VC) group. The HT-29 cell-bearing mice exhibited an M2-polarized immune balance based on the TNF-α (M1)/IL-10 (M2) cytokine secretion ratio by macrophages compared to that in the VC group. Notably, low-dose CA administration significantly (P < 0.05) increased the TNF-α/IL-10 cytokine secretion ratio compared to that in the DC group, evidencing that low-dose CA administration reversed the immune response toward the M1-polarized immune balance in the HT-29 cell-bearing mice. CA administration may restore the M1-polarized immune balance but decrease serum IgG and IgM levels in subjects with colorectal cancer cells.

Cysteine fluorescent probes are specialized molecular tools that facilitate highly sensitive detection of cysteine via alterations in fluorescent signals. Currently, these probes have been widely employed in fields including disease biomarker monitoring, redox balance research, and drug toxicity assessment, thereby exhibiting substantial application potential in biochemical and biomedical studies. In this study, a novel fluorescent probe was designed for detecting cysteine based on the thiopyrone structure. Through characterization of its properties, it was found that this fluorescent probe exhibits a large Stokes shift (217 nm), excellent sensitivity (13.60 nM), rapid response time (3.0 min), high stability and selectivity. Furthermore, this cysteine fluorescent probe demonstrates excellent applications in RAW 264.7 cells, zebrafish, and actual samples. This study also proposes a more convenient method for testing cysteine levels using mobile phone software, and the findings indicate that the fluorescent probe under investigation has considerable potential for use in cysteine detection.