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Water-permeable hollow starch particles alter the rheological behavior of their granular suspensions. However, their thin shells can rupture limiting applications. In this study, we used amaranth starch as building blocks (1 µm) to craft a crosslinked superstructure. Pickering emulsions were used as the templates where starch coated the droplets. Emulsions were heated at 75 °C to induce interpenetration of the polymers followed by precipitation in ethanol to trigger colloidal fusion. Particles were then crosslinked by sodium tri-metaphosphate; hollow particles formed after the interior template was removed by hexane. When canola oil was used, the particles ruptured at pH 11.5 due to the repulsion between the strands. In contrast, palm oil, emulsified at 50 °C, formed a rigid core after cooling, locked the starch at the surface and retained the structure. The crosslinked colloidosomes were larger (89 µm) and exhibited higher viscosity, and stronger stability. Larger particles (>100 µm) were produced using higher templating volume. Gentle centrifugation to harvest the particles kept the shells intact. The hollow structure exhibited jamming transition above 10 w/w%, which could serve as a super-thickener. This work demonstrates that microarchitecture plays a critical role in shaping material functionality.
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In this study, the biodegradation of various natural rubber (NR) samples, i.e., neat NR and NR filled with two different curative contents was investigated under a long-term simulated soil condition at a temperature of 25 ± 2 °C in accordance with ISO 17556. Natural clay loam soil, with a pH of 7.2 and a water holding capacity of 57.6%, was employed. Under controlled test condition both unvulcanized and vulcanized NR samples having low curative content, respectively designated as UNRL and VNRL, exhibited similar biodegradation behaviors to the neat NR. They showed fast biodegradation at the early stage, and their biodegradation rate did not significantly change throughout the test period (365 days). However, for the NR samples having high curative content, respectively called UNRH and VNRH for the unvulcanized and vulcanized samples, a biodegradation delay was observed within the first 130 days. Surprisingly, the UNRH showed a relatively high biodegradation rate after the induction period. At the end of the test, most of the rubber samples (the neat NR, UNRL, VNRL, and UNRH) showed a comparable degree of biodegradation, with a value ranging from 54-59%. The VNRH, on the other hand, showed the lowest degree of biodegradation (ca. 28%). The results indicate that the number of curatives does not significantly affect the biodegradability of unvulcanized NR in the long term, despite the fact that a high curative content might retard microorganism activity at the beginning of the biodegradation process. Apparently, crosslink density is one of the key factors governing the biodegradability of NR. The phytotoxicity of the soils after the biodegradation test was also assessed and represented in terms of seedling emergence, survival rate, and plant biomass for Sorghum bicolor. The values of seedling emergence (≥80%), survival rate (100%), and plant biomass of all soil samples were not statistically different from those of the blank soil, indicating the low phytotoxicity of the tested soils subjected to the biodegradation of the rubber samples. Taken as a whole, it can be concluded that the CO2 measurement technique is one of the most effective methods to assess the biodegradability of rubbers. The knowledge obtained from this study can also be applied to formulate more environmentally friendly rubber products.
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Transcription reprogramming is essential to carry out a variety of cell dynamics such as differentiation and stress response. During reprogramming of transcription, a number of adverse effects occur and potentially compromise genomic stability. Formaldehyde as an obligatory byproduct is generated in the nucleus via oxidative protein demethylation at regulatory regions, leading to the formation of DNA crosslinking damage. Elevated levels of transcription activities can result in the accumulation of unscheduled R-loop. DNA strand breaks can form if processed 5-methylcytosines are exercised by DNA glycosylase during imprint reversal. When cellular differentiation involves a large number of genes undergoing transcription reprogramming, these endogenous DNA lesions and damage-prone structures may pose a significant threat to genome stability. In this review, we discuss how DNA damage is formed during cellular differentiation, cellular mechanisms for their removal, and diseases associated with transcription reprogramming.
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Reprogramación Celular , Daño del ADN , Transcripción Genética , Humanos , Animales , Reparación del ADN , Diferenciación Celular , Inestabilidad GenómicaRESUMEN
Self-protective carbonized polymer dots (CPDs) with advantageous crosslinked nano-structures have attracted considerable attention in metal-free room temperature phosphorescence (RTP) materials, whereas, their RTP emissions are still limited to short wavelength. Expanding their RTP emission to Near-Infrared (NIR) range is attractive but suffers from the difficulties in constructing narrow energy levels and inhibiting intense nonradiative decay. Herein, a crosslink-enhanced emission (CEE)-dominated construction strategy was proposed, achieving desired NIR RTP (710 nm) in self-protective CPDs for the first time. Structural factors, i.e.ï¼crosslinking (covalent-bond CEE), conjugation (conjugated amine with bridging N-H and C=C group), and steric hindrance (confined-domain CEE), were confirmed indispensable for triggering NIR RTP emission in CPDs. Contrast experiments and theoretical calculations further revealed the rationality of the design strategy originating from CEE in terms of promoting the narrow energy level emission of triplet excitons and inhibiting the nonradiative quenching. This work not only firstly achieves NIR RTP in self-protective CPDs, but also helps understand the NIR RTP origin to further guide the synthesis of diverse CPDs with efficient long-wavelength RTP emission.
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Histone modification is one of the key elements in epigenetic control and plays important roles in regulation of biological processes and disease development. Currently, records of human histone modifications with various levels of confidence in evidence are scattered in various knowledgebases and databases. In the present study, a curated catalogue of human histone modifications, CHHM, was obtained by manual retrieval, evidence assessment, and integration of modification records from 10 knowledgebases/databases and 3 complementary articles. CHHM contains 6612 nonredundant modification entries covering 31 types of modifications (including 9 types of emerging modifications) and 2 types of histone-DNA crosslinks, that were identified in 11 H1 variants, 21 H2A variants, 21 H2B variants, 9 H3 variants, and 2 H4 variants. For ease of visualization and accessibility, modification entries are presented with aligned protein sequences in an Excel file. Confidence level in evidence is provided for each entry. Acylation modifications contribute to the highest number of modification entries in CHHM. This supports that cellular metabolic status plays a very important role in epigenetic control. CHHM reveals modification hotspot regions and uneven distribution of the modification entries across the histone families. Such uneven distribution may suggest that a particular histone family is more susceptible to certain types of modifications. CHHM not only serves as an important and user-friendly resource for biomedical and clinical researches involving histone modifications and transcriptional regulation, but also provides new insights for basic researches in the mechanism of human histone modifications and epigenetic control.
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Código de Histonas , Histonas , Humanos , Histonas/metabolismo , Histonas/genética , Epigénesis Genética , Procesamiento Proteico-PostraduccionalRESUMEN
OBJECTIVE: When using the cortical bone trajectory (CBT) technique, two technical countermeasures are recommended to promote bone fusion: taking a long CBT screw path directed more anteriorly and improving the stability of the spinal construct by facet joint preservation, cross-link augmentation, and rigid anterior interbody reconstruction. However, there has been no report on how these surgical procedures, which are heavily dependent on the surgeon's preference, contribute to successful bone fusion. The aim of the present study was to investigate the progression of lumbar spinal fusion using the long CBT technique and identify factors contributing to the time taken to achieve bone fusion, with a particular focus on the involvement of surgical procedures. METHODS: A total of 167 consecutive patients with L4 degenerative spondylolisthesis who underwent single-level posterior lumbar interbody fusion at L4-5 using the long CBT technique were included (mean follow-up 42.8 months). Bone fusion was assessed to identify factors contributing to the time to achieve bone fusion. Investigated factors were 1) age, 2) sex, 3) BMI, 4) bone mineral density, 5) intervertebral mobility, 6) screw depth in the vertebra, 7) extent of facetectomy, 8) cross-link augmentation, 9) cage material, 10) cage design, 11) number of cages, and 12) contact area of cages with the vertebral endplate. RESULTS: The bone fusion rate was 89.2% at 2 years postoperatively and 95.8% at the last follow-up, with a mean period to bone fusion of 16.6 ± 9.6 months. Multivariate regression analysis revealed that age (standardized regression coefficient [ß] = 0.25, p = 0.002), female sex (ß = -0.22, p = 0.004), and BMI (ß = 0.15, p = 0.045) were significant independent factors affecting the time to achieve bone fusion. There was no significant effect of surgical procedures (p ≥ 0.364). CONCLUSIONS: This is the first study to investigate the progression of lumbar spinal fusion using the long CBT technique and identify factors contributing to the time taken to achieve bone fusion. Patient factors such as age, sex, and BMI affected the progression of bone fusion, and surgical factors had only weak effects.
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Genomic interstrand crosslinks (ICLs) are formed by reactive species generated during normal cellular metabolism, produced by the microbiome, and employed in cancer chemotherapy. While there are multiple options for replication dependent and independent ICL repair, the crucial step for each is unhooking one DNA strand from the other. Much of our insight into mechanisms of unhooking comes from powerful model systems based on plasmids with defined ICLs introduced into cells or cell free extracts. Here we describe the properties of exogenous and endogenous ICL forming compounds and provide an historical perspective on early work on ICL repair. We discuss the modes of unhooking elucidated in the model systems, the concordance or lack thereof in drug resistant tumors, and the evolving view of DNA adducts, including ICLs, formed by metabolic aldehydes.
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Aductos de ADN , Reparación del ADN , Humanos , Aductos de ADN/metabolismo , ADN/metabolismo , Daño del ADN , Animales , Reactivos de Enlaces Cruzados , Neoplasias/genética , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Replicación del ADNRESUMEN
Lysyl hydroxylase 2 (LH2) catalyzes the hydroxylation of lysine residues in the telopeptides of type I collagen. This modification is critical for the formation of stable hydroxylysine-aldehyde derived collagen cross-links, thus, for the stability of collagen fibrils. Though dysfunction of LH2 causes Bruck syndrome, recessive osteogenesis imperfecta with joint contracture, the molecular mechanisms by which LH2 affects bone formation are still not well understood. Since the Plod2 knockout mice are embryonically lethal, we generated bone-specific LH2 conditional knockout mice (bsLH2-cKO) using the osteocalcin-Cre/loxP system, and evaluated phenotypes of femurs. LH2 mRNA and protein levels assessed by qPCR, immunohistochemistry and Data Independent Acquisition proteomics were all markedly low in bsLH2-cKO femurs when compared to controls. Lysine hydroxylation of both carboxy- and amino-terminal telopeptides of an α1(I) chain were significantly diminished resulting in reduction of the hydroxylysine-aldehyde derived cross-links. The collagen fibrils in bsLH2-cKO appeared to be thicker, often fused and irregular when compared to controls. In addition, bone mineral density and mechanical properties of bsLH2-cKO femurs were significantly impaired. Taken together, these data demonstrate that LH2-catalyzed modification and consequent cross-linking of collagen are critical for proper bone formation and mechanical strength.
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Since the report of "DNA untwisting" activity in 1972, â¼50 years of research has revealed seven topoisomerases in humans (TOP1, TOP1mt, TOP2α, TOP2ß, TOP3α, TOP3ß and Spo11). These conserved regulators of DNA topology catalyze controlled breakage to the DNA backbone to relieve the torsional stress that accumulates during essential DNA transactions including DNA replication, transcription, and DNA repair. Each topoisomerase-catalyzed reaction involves the formation of a topoisomerase cleavage complex (TOPcc), a covalent protein-DNA reaction intermediate formed between the DNA phosphodiester backbone and a topoisomerase catalytic tyrosine residue. A variety of perturbations to topoisomerase reaction cycles can trigger failure of the enzyme to re-ligate the broken DNA strand(s), thereby generating topoisomerase DNA-protein crosslinks (TOP-DPC). TOP-DPCs pose unique threats to genomic integrity. These complex lesions are comprised of structurally diverse protein components covalently linked to genomic DNA, which are bulky DNA adducts that can directly impact progression of the transcription and DNA replication apparatus. A variety of genome maintenance pathways have evolved to recognize and resolve TOP-DPCs. Eukaryotic cells harbor tyrosyl DNA phosphodiesterases (TDPs) that directly reverse 3'-phosphotyrosyl (TDP1) and 5'-phoshotyrosyl (TDP2) protein-DNA linkages. The broad specificity Mre11-Rad50-Nbs1 and APE2 nucleases are also critical for mitigating topoisomerase-generated DNA damage. These DNA-protein crosslink metabolizing enzymes are further enabled by proteolytic degradation, with the proteasome, Spartan, GCNA, Ddi2, and FAM111A proteases implicated thus far. Strategies to target, unfold, and degrade the protein component of TOP-DPCs have evolved as well. Here we survey mechanisms for addressing Topoisomerase 1 (TOP1) and Topoisomerase 2 (TOP2) DPCs, highlighting systems for which molecular structure information has illuminated function of these critical DNA damage response pathways.
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Reparación del ADN , Humanos , ADN/metabolismo , ADN-Topoisomerasas de Tipo I/metabolismo , ADN-Topoisomerasas de Tipo I/química , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/química , ADN-Topoisomerasas/metabolismo , Daño del ADN , ADN-Topoisomerasas de Tipo II/metabolismo , Replicación del ADNRESUMEN
This study comprehensively explored the helix-stabilizing effects of amine-bearing hydrocarbon cross-links (ABXs), revealing their context-dependent nature influenced by various structural parameters. Notably, we identified a 9-atom ABX as a robust helix stabilizer, showcasing versatile synthetic adaptability while preserving peptide water solubility. Future investigations are imperative to fully exploit this system's potential and enrich our chemical toolkit for designing innovative peptide-based biomolecules.
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Aminas , Hidrocarburos , Interacciones Hidrofóbicas e Hidrofílicas , Péptidos , Péptidos/química , Péptidos/síntesis química , Aminas/química , Aminas/síntesis química , Hidrocarburos/química , Hidrocarburos/síntesis química , Estructura Molecular , Solubilidad , Reactivos de Enlaces Cruzados/química , Reactivos de Enlaces Cruzados/síntesis químicaRESUMEN
This study investigates the storage life of particle-filled polymer composites (PFPCs) under the influence of aging effects. High-temperature accelerated aging tests were conducted at 60 °C, 70 °C, and 80 °C for various days to analyze the impact of aging time and temperature on the mechanical behavior of the materials. A predictive model for crosslink density was established using the Arrhenius equation, and the relationship between crosslink density and relaxation modulus was determined based on polymer physics theory. On this basis, a viscoelastic constitutive model that incorporates aging effects was developed. Structural analyses of a PFPC column with a length of 2.3 m and outer diameter of 1.8 m were performed using the UMAT subroutine in ABAQUS. Subsequently, a safety margin assessment method based on dewetting strain was employed to predict the storage life of the PFPC column. The results indicate that the aging viscoelastic constitutive model effectively characterizes the hardening effects caused by aging in the composites during storage. The storage life for the PFPC column considering aging effects decreases from 22 years to 19 years compared to models that ignore such effects. This approach provides a reference for estimating the storage life of PFPC columns considering aging effects.
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The Fanconi anemia (FA) repair pathway governs repair of highly genotoxic DNA interstrand crosslinks (ICLs) and relies on translesion synthesis (TLS). TLS is facilitated by REV1 or site-specific monoubiquitination of proliferating cell nuclear antigen (PCNA) (PCNA-Ub) at lysine 164 (K164). A PcnaK164R/K164R but not Rev1-/- mutation renders mammals hypersensitive to ICLs. Besides the FA pathway, alternative pathways have been associated with ICL repair (1, 2), though the decision making between those remains elusive. To study the dependence and relevance of PCNA-Ub in FA repair, we intercrossed PcnaK164R/+; Fancg-/+ mice. A combined mutation (PcnaK164R/K164R; Fancg-/- ) was found embryonically lethal. RNA-seq of primary double-mutant (DM) mouse embryonic fibroblasts (MEFs) revealed elevated levels of replication stress-induced checkpoints. To exclude stress-induced confounders, we utilized a Trp53 knock-down to obtain a model to study ICL repair in depth. Regarding ICL-induced cell toxicity, cell cycle arrest, and replication fork progression, single-mutant and DM MEFs were found equally sensitive, establishing PCNA-Ub to be critical for FA-ICL repair. Immunoprecipitation and spectrometry-based analysis revealed an unknown role of PCNA-Ub in excluding mismatch recognition complex MSH2/MSH6 from being recruited to ICLs. In conclusion, our results uncovered a dual function of PCNA-Ub in ICL repair, i.e. exclude MSH2/MSH6 recruitment to channel the ICL toward canonical FA repair, in addition to its established role in coordinating TLS opposite the unhooked ICL.
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Facing the severe problem of microplastic pollution, there is an urgent need to develop biodegradable fibers to replace the petrochemical fibers. Sodium alginate, a biomass polysaccharide, has gained widespread attentions recently for the fiber manufacture. However, the limited mechanical strength of alginate fibers restricts their usages as load-bearing fabrics and reinforcement fibers. Here, we develop a novel strategy to prepare alginate multifilaments using pre-crosslinked sodium alginate solutions. The increase in the pre-crosslinking ratio effectively hinders the disentanglement of sodium alginate chains at high stretches, causing an increase in the shear viscosity of the solution ascertained from the capillarity-driven thinning process from 4.5 Pa·s to 9.9 Pa·s and facilitating the high alignment and orientation of sodium alginate chains. The resultant fibers possess a breaking strength of 474 MPa, elongation at break of 16 %, Young's modulus of 14.4 GPa, and toughness of 51.8 MJ/m3, exceeding most biomass fibers without reinforcement additives. The high orientation degree of 0.865 and high spinnability of alginate multifilaments enable their applications in multi-channel encryption fabrics that exhibit distinct information under various optical conditions. This rheological regulation of spinning solutions provides a facile yet effective strategy to enhance the mechanical performance and broaden application scenarios of alginate fibers.
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Solution styrene-butadiene rubber (SSBR) is widely used to improve the properties of tire tread compounds. Tire wear particles (TWPs), which are generated on real roads as vehicles traverse, represent one of significant sources of microplastics. In this study, four SSBR compounds were prepared using two SSBRs with high styrene (STY samples) and 1,2-unit (VIN samples) contents, along with dicyclopentadiene resin. The abrasion behaviors were investigated using four different abrasion testers: cut and chip (CC), Lambourn, DIN, and laboratory abrasion tester (LAT100). The abrasion rates observed in the Lambourn and LAT100 abrasion tests were consistent with each other, but the results of CC and DIN abrasion tests differed from them. The addition of the resin improved the abrasion rate and resulted in the generation of large wear particles. The abrasion rates of STY samples in the Lambourn and LAT100 abrasion tests were lower than those of VIN samples, whereas the values in the CC and DIN abrasion tests were higher than those of VIN samples. The wear particles were predominantly larger than 1000 µm, except for the VIN sample in the DIN abrasion test. However, TWPs > 1000 µm are rarely produced on real roads. The size distributions of wear particles > 1000 µm were 74.0-99.5%, 65.9-93.4%, 7.2-95.1%, and 37.5-83.0% in the CC, Lambourn, DIN, and LAT100 abrasion tests, respectively. The size distributions of wear particles in the Lambourn and LAT100 abrasion tests were broader than those in the other tests, whereas the distributions in the CC abrasion test were narrower. The abrasion patterns and the morphologies and size distributions of wear particles generated by the four abrasion tests varied significantly, attributable to differences in the bound rubber contents, crosslink densities, and tensile properties.
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One method to improve the properties of covalent adaptable networks (CANs) is to reinforce them with a fraction of permanent cross-links without sacrificing their (re)processability. Here, a simple method to synthesize poly(n-hexyl methacrylate) (PHMA) and poly(n-lauryl methacrylate) (PLMA) networks containing static dialkyl disulfide cross-links (utilizing bis(2-methacryloyl)oxyethyl disulfide, or DSDMA, as a permanent cross-linker) and dynamic dialkylamino sulfur-sulfur cross-links (utilizing BiTEMPS methacrylate as a dissociative dynamic covalent cross-linker) is presented. The robustness and (re)processability of the CANs are demonstrated, including the full recovery of cross-link density after recycling. The authors also investigate the effect of static cross-link content on the stress relaxation responses of the CANs with and without percolated, static cross-links. As PHMA and PLMA have very different activation energies of their respective cooperative segmental mobilities, it is shown that the dissociative CANs without percolated, static cross-links have activation energies of stress relaxation that are dominated by the dissociation of BiTEMPS methacrylate cross-links rather than by the cooperative relaxations of backbone segments, i.e., the alpha relaxation. In CANs with percolated, static cross-links, the segmental relaxation of side chains, i.e., the beta relaxation, is critical in allowing for large-scale stress relaxation and governs their activation energies of stress relaxation.
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Skin could protect our body and regenerate itself to against dysfunctional and disfiguring scars when faced with external injury. As wound dressings, hydrogels are biocompatible, hydrophilic and have a 3D structure similar to the extracellular matrix (ECM). In particular, hydrogels with drug-releasing capabilities are in acute wound healing. In this paper, photocrosslinked hydrogels served as wound dressing based on sodium carboxymethylcellulose (CMC) were prepared to promote wound healing. Photocrosslinked hydrogels were prepared by grafting lysine and allyl glycidyl ether (AGE) onto CMC and encapsulating curcumin (Cur). The synthesized hydrogels had the unique 3D porous structure with a swelling ratio up to 1300 % in aqueous solution. The drug release ratios of the hydrogels were 20.8 % in acid environment, and 14.4 % in alkaline environment. Notably, the hydrogels showed good biocompatibility and antibacterial properties and also exhibited the ability to accelerate the process of skin wound healing while prevent inflammation and scar formation when applied to a mouse skin wound model. As a result, the prepared hydrogels Gel-CLA@Cur showed great potential in wound healing.
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Carboximetilcelulosa de Sodio , Curcumina , Hidrogeles , Cicatrización de Heridas , Curcumina/farmacología , Curcumina/química , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/síntesis química , Cicatrización de Heridas/efectos de los fármacos , Carboximetilcelulosa de Sodio/química , Animales , Ratones , Liberación de Fármacos , Antibacterianos/farmacología , Antibacterianos/química , Portadores de Fármacos/química , Reactivos de Enlaces Cruzados/química , Piel/efectos de los fármacos , Sistemas de Liberación de MedicamentosRESUMEN
Mixed tin-lead (Sn-Pb) perovskites have attracted the attention of the community due to their narrow bandgap, ideal for photovoltaic applications, especially tandem solar cells. However, the oxidation and rapid crystallization of Sn2+ and the interfacial traps hinder their development. Here, cross-linkable [6,6]-phenyl-C61-butyric styryl dendron ester (C-PCBSD) is introduced during the quenching step of perovskite thin film processing to suppress the generation of surface defects at the electron transport layer interface and improve the bulk crystallinity. The C-PCBSD has strong coordination ability with Sn2+ and Pb2+ perovskite precursors, which retards the crystallization process, suppresses the oxidation of Sn2+, and improves the perovskite bulk and surface crystallinity, yielding films with reduced nonradiative recombination and enhanced interface charge extraction. Besides, the C-PCBSD network deposited on the perovskite surface displays superior hydrophobicity and oxygen resistance. Consequently, the devices with C-PCBSD obtain PCEs of up to 23.4% and retained 97% of initial efficiency after 2000 h of storage in a N2 atmosphere.
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DNA-protein crosslinks (DPCs) are highly toxic DNA lesions represented by proteins covalently bound to the DNA. Persisting DPCs interfere with fundamental genetic processes such as DNA replication and transcription. Cytidine analog zebularine (ZEB) has been shown to crosslink DNA METHYLTRANSFERASE1 (MET1). Recently, we uncovered a critical role of the SMC5/6-mediated SUMOylation in the repair of DPCs. In an ongoing genetic screen, we identified two additional candidates, HYPERSENSITIVE TO ZEBULARINE 2 and 3, that were mapped to REGULATOR OF TELOMERE ELONGATION 1 (RTEL1) and polymerase TEBICHI (TEB), respectively. By monitoring the growth of hze2 and hze3 plants in response to zebularine, we show the importance of homologous recombination (HR) factor RTEL1 and microhomology-mediated end-joining (MMEJ) polymerase TEB in the repair of MET1-DPCs. Moreover, genetic interaction and sensitivity assays showed the interdependency of SMC5/6 complex, HR, and MMEJ in the homology-directed repair of MET1-DPCs in Arabidopsis. Altogether, we provide evidence that MET1-DPC repair in plants is more complex than originally expected.
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Proteínas de Arabidopsis , Arabidopsis , Citidina , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Citidina/análogos & derivados , Citidina/metabolismo , Citidina/farmacología , Reparación del ADN por Recombinación , Reparación del ADN , ADN de Plantas/genética , ADN de Plantas/metabolismo , Daño del ADNRESUMEN
Breast cancer has now replaced lung cancer as the most prevalent malignant tumor worldwide, posing a serious health risk to women. We have recently designed a promising option strategy for the treatment of breast cancer. In this work, cyclodextrin metal-organic frameworks with high drug-carrying properties were endo-crosslinked by 3,3'dithiodipropionyl chloride to form cubic phase gel nanoparticles, which were drug-loaded and then coated by MCF-7 cell membranes. After intravenous injection, this multifunctional nanomedicine achieved dramatically homologous targeting co-delivery of honokiol and indocyanine green to the breast tumor. Further, the disulfide bonds in the nanostructures achieved glutathione-responsive drug release, induced tumor cells to produce reactive oxygen species and promoted apoptosis, resulting in tumor necrosis, and at the same time, inhibited Ki67 protein expression, which enhanced photochemotherapy, and resulted in a 94.08 % in vivo tumor suppression rate in transplanted tumor-bearing mice. Thereby, this nanomimetic co-delivery system may have a place in breast cancer therapy due to its simple fabrication process, excellent biocompatibility, efficient targeted delivery of insoluble drugs, and enhanced photochemotherapy.
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Compuestos de Bifenilo , Neoplasias de la Mama , Liberación de Fármacos , Glutatión , Verde de Indocianina , Lignanos , Estructuras Metalorgánicas , Fotoquimioterapia , Verde de Indocianina/administración & dosificación , Verde de Indocianina/química , Animales , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Células MCF-7 , Fotoquimioterapia/métodos , Compuestos de Bifenilo/administración & dosificación , Compuestos de Bifenilo/química , Estructuras Metalorgánicas/química , Glutatión/metabolismo , Lignanos/administración & dosificación , Lignanos/química , Lignanos/farmacología , Ratones Endogámicos BALB C , Ciclodextrinas/química , Ratones , Apoptosis/efectos de los fármacos , Nanopartículas/química , Nanopartículas/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Especies Reactivas de Oxígeno/metabolismo , Ratones Desnudos , Portadores de Fármacos/química , Compuestos Alílicos , FenolesRESUMEN
Superior multifunctional hydrogel dressings are of considerable interest in wound healing. In clinical practice, it is useful to investigate hydrogel dressings that offer multifunctional benefits to expedite the process of wound healing. In this study, Catechol-grafted Chitosan, Gelatin, and Fe3+ as substrates to construct a hydrogel network. The network was dynamically cross-linked to form Ccg@Fe hydrogel substrate. Fe3O4 nanoparticles and baicalin, which possess antimicrobial and anti-inflammatory properties, were loaded onto the substrate to form a photothermal antibacterial composite hydrogel dressing (Ccg@Fe/Bai@Fe3O4 NPs). The Ccg@Fe hydrogel was characterised using Fourier transform infrared spectroscopy (FTIR) and Ultraviolet-visible spectrophotometry (UV-Vis). The morphological, mechanical, and adhesion properties of the hydrogel were determined using scanning electron microscopy (SEM) and a universal testing machine. The hydrogel's swelling, hemostasis, and self-healing properties were also evaluated. Additionally, the study determined the release rate of hydrogel-loaded antimicrobial and anti-inflammatory Baicalin (Ccg@Fe/Bai) and evaluated the photothermal antimicrobial properties of hydrogel-loaded Fe3O4 nanoparticles (Ccg@Fe/Bai@Fe3O4 NPs) through synergistic photothermal therapy (PTT). Histological staining of mice skin wound tissues using Masson and H&E revealed that the Ccg@Fe/Bai@Fe3O4 NPs hydrogel dressing demonstrated potential healing ability with the aid of PTT. The study suggests that this multifunctional hydrogel dressing has great potential for wound healing.