Size-dependent toxicity of polystyrene microplastics on the gastrointestinal tract: Oxidative stress related-DNA damage and potential carcinogenicity.

Microplastics (MPs) and nanoplastics (NPs) have been generally regarded as emerging pollutants and received worldwide attention in recent years. Water and food consumption are the primary pathways for human exposure to MPs/NPs, thus gastrointestinal tracts may be susceptible to their toxicity. Although the recent report has indicated the presence of MPs/NPs in multiple human organs, little is known about their gastric effects. Therefore, this study focused on the adverse effects of polystyrene microplastics (PS-MPs) on gastric epithelium in vivo and in vitro. Surface-enhanced Raman spectroscopy (SERS) revealed the distribution of PS-MPs was associated with their particle sizes, and predominantly concentrated in gastric tissues. Gastric barrier injury and mitochondrial damage were observed in rats after exposure to PS-MPs. Compared with the larger ones, polystyrene nanoplastics (PS-NPs) more significantly reduced the activity of antioxidant enzymes while enhancing the level of MDA, 8-OhdG and γ-H2AX. Meanwhile, PS-MPs caused upregulation of ß-catenin/YAP through redox-dependent regulation of nucleoredoxin (NXN) and dishevelled (Dvl). These findings supported the size-dependent effects of PS-MPs on oxidative stress and DNA damage. Moreover, the redox-dependent activation of the ß-catenin/YAP cascade suggested a novel toxic mechanism for PS-MPs and implied the potential carcinogenic effects.

Enhanced physiochemical, antibacterial, and hemostatic performance of collagen-quaternized chitosan-graphene oxide sponges for promoting infectious wound healing.

Bacteria-infected wound healing has attracted widespread attention in biomedical engineering. Wound dressing is a potential strategy for repairing infectious wounds. However, the development of wound dressing with appropriate physiochemical, antibacterial, and hemostatic properties, remains challenging. Hence, there is a motivation to develop new synthetic dressings to improve bacteria-infected wound healing. Here, we fabricate a biocompatible sponge through the covalent crosslinking of collagen (Col), quaternized chitosan (QCS), and graphene oxide (GO). The resulting Col-QCS-GO sponge shows an elastic modulus of 1.93-fold higher than Col sponge due to enhanced crosslinking degree by GO incorporation. Moreover, the fabricated Col-QCS-GO sponge shows favorable porosity (84.30 ± 3.12 %), water absorption / retention (2658.0 ± 113.4 % / 1114.0 ± 65.7 %), and hemostasis capacities (blood loss <50.0 mg). Furthermore, the antibacterial property of the Col-QCS-GO sponge under near-infrared (NIR) irradiation is significantly enhanced (the inhibition rates are 99.9 % for S. aureus and 99.9 % for E. coli) due to the inherent antibacterial properties of QCS and the photothermal antibacterial capabilities of GO. Finally, the Col-QCS-GO+NIR sponge exhibits the lowest percentage of wound area (9.05 ± 1.42 %) at day 14 compared to the control group (31.61 ± 1.76 %). This study provides new insights for developing innovative sponges for bacteria-infected wound healing.

Visible-light-induced disruption of diselenide-containing layer-by-layer films: toward combination of chemotherapy and photodynamic therapy.

A photoresponsive polyelectrolyte multilayer film containing a diselenide functional group is fabricated using an unconventional layer-by-layer method. The polycation backbone is constructed through copolymerization of di-(1-hydroxylundecyl) diselenide and 1,4-bis(2-hydroxyethyl)piperazine with 2,4-diisocyanatotoluene. A common polyanion poly(styrene sulfonate) is selected as the polyanion. The obtained film can be gradually disrupted under the irradiation of mild visible light, and this process can be monitored with UV-vis spectroscopy. The residue of the film is estimated to be 17% after 5 h of irradiation. The intensity of the visible light can be as low as 50 mW cm⁻², which is even weaker than the sunlight. The cytotoxicity of the building blocks is evaluated in MTT assays using human hepatic cell line (L-02), and the results are satisfactory. Further tests show that cells can grow in a regular manner on this film, indicating good biocompatibility. In addition, the film can be used to achieve cargo loading and controlled release. Considering that light can not only trigger controlled release but also act as part of the therapy itself (photodynamic therapy), this system shows hope for further development into a platform for the combination of chemotherapy and photodynamic therapy, especially for applications concerning skin.

The detrimental effects of micro-and nano-plastics on digestive system: An overview of oxidative stress-related adverse outcome pathway.

With the massive manufacture and use of plastics, plastic pollution-related environmental impacts have raised great concern in recent years. As byproducts of plastic fragmentation and degradation, microplastics (MPs) and nanoplastics (NPs) have been identified as novel pollutants that posed a threat to the ecosystem and humans. Since MPs/NPs could be transported via the food chain and retained in the water, the digestive system should be one of the major targets of MPs/NPs-related toxicity. Although considerable evidence has supported the digestive toxicity of MPs/NPs, the proposed mechanisms remained ambiguous due to the variety of study types, models, and endpoints. This review provided a mechanism-based perspective on MPs/NPs-induced digestive effects by adopting the adverse outcome pathway framework as a promising tool. The overproduction of reactive oxygen species was identified as the molecular initiating event in MPs/NPs-mediated injury to the digestive system. A series of detrimental effects including oxidative stress, apoptosis, inflammation, dysbiosis, and metabolic disorders were summarized as key events. Finally, the occurrence of these effects eventually led to an adverse outcome, suggesting a possible increase in the incidence of digestive morbidity and mortality.

Graphene Oxide Functionalized Gelatin Methacryloyl Microgel for Enhanced Biomimetic Mineralization and in situ Bone Repair.

Introduction: The formation of bone-like apatite (Ap) on natural polymers through biomimetic mineralization using simulated body fluid (SBF) can improve osteoconductivity and biocompatibility, while lowering immunological rejection. Nonetheless, the coating efficiency of the bone-like Ap layer on natural polymers requires improvement. Carbonyls (-COOH) and hydroxyls (-OH) are abundant in graphene oxide (GO), which may offer more active sites for biomimetic mineralization and promote the proliferation of rat bone marrow stromal cells (BMSCs). Methods: In this study, gelatin methacryloyl (GelMA) microgels were infused with GO (0, 0.5, 1, and 2 mg/mL) and embedded into microgels in SBF for 1, 7, and 14 days. Systematic in vitro and in vivo experiments were performed to evaluate the structure of the microgel and its effect on cell proliferation and ability to repair bone defects in rats. Results: The resulting GO-GelMA-Ap microgels displayed a porous, interconnected structure with uniformly coated surfaces in bone-like Ap, and the Ca/P ratio of the 1 mg/mL GO-GelMA-Ap group was comparable to that of natural bone tissue. Moreover, the 1 mg/mL GO-GelMA-Ap group exhibited a greater Ap abundance, enhanced proliferation of BMSCs in vitro and increased bone formation in vivo compared to the GelMA-Ap group. Discussion: Overall, this study offers a novel method for incorporating GO into microgels for bone tissue engineering to promote biomimetic mineralization.

Radiation-sensitive diselenide block co-polymer micellar aggregates: toward the combination of radiotherapy and chemotherapy.

We have developed a potential radiation-sensitive drug-delivery system using active diselenide-containing block co-polymer aggregates in aqueous solution that can load and release anticancer drugs. These aggregates were sensitive to even a low dose of γ-radiation, such as 5 Gy, which is close to the radiation dose received by patients during a single radiotherapy treatment. This line of research may open an avenue for the combination of radiotherapy and chemotherapy.

Block ionomer complex micelles based on the self-assembly of poly(ethylene glycol)-block-poly(acrylic acid) and CdCl2 for anti-tumor drug delivery.

A novel block ionomer complex micelles as drug carrier is developed utilizing self-assemble of poly(ethylene glycol)-block-poly(acrylic acid) (PEG-b-PAA) and cadmium chloride. This micelles are characterized to be have good bio-compatibility, hydrophilicity, passive targeting and sustained slow release property which shows great potential for liver cancer therapy. Block ionomer complex micelles based on PEG-b-PAA and cadmium chloride can self-assemble in distilled water, and Cd(²+) agent is entrapped into the core stabilized by PEG shells. Results showed the block ionomer complex micelles to be spherically shaped. Cadmium was incorporated easily into the ionic core with remarkably high efficiency (34.25% weight (wt)/wt). The cadmium-loaded polymeric micelles exhibited sustained and slow release behavior of cadmium and a potent cytotoxicity against SMMC-7721 in vitro. This novel block ionomer complex micelles with cores of metal antitumor drug indicates to be potential carriers for effective drug delivery.

Exposure to polydopamine nanoparticles induces neurotoxicity in the developing zebrafish.

Currently, the potential applications of polydopamine (PDA) nanoparticles in the biomedical field are being extensively studied, such as cell internalization, biocompatible surface modification, biological imaging, nano-drug delivery, cancer diagnosis, and treatment. However, the subsequent toxicological response to PDA nanoparticles, especially on nervous system damage was still largely unknown. In this regard, the evaluation of the neurotoxicity of PDA nanoparticles was performed in the developing zebrafish larvae. Results of the transmission electron microscope (TEM), diameter analysis, 1H NMR, and thermogravimetric analysis (TGA) indicated that PDA nanoparticles had high stability without any depolymerization; the maximum non-lethal dose (MNLD) and LD10 of PDA nanoparticles for zebrafish were determined to be 0.5 mg/mL and 4 mg/mL. Pericardial edema and uninflated swim bladders were observed in zebrafish larvae after exposure to PDA nanoparticles. At a concentration higher than MNLD, the fluorescence images manifested that the PDA nanoparticles could inhibit the axonal growth of peripheral motor neurons in zebrafish, which might affect the movement distances and speed, disturb the movement trace, finally resulting in impaired motor function. However, in further investigating the mechanism of PDA nanoparticles-induced neurotoxicity in zebrafish larvae, we did not find apoptosis of central neurocytes. Our data suggested that PDA nanoparticles might trigger neurotoxicity in zebrafish, which could provide an essential clue for the safety assessment of PDA nanoparticles.

Cardiovascular toxicity assessment of polyethylene nanoplastics on developing zebrafish embryos.

Environmental exposure to nanoplastics is inevitable as the application of nanoplastics in our daily life is more and more extensively. So, the adverse effects of nanoplastics on human health are also gaining greater concerns. However, the subsequent toxicological response to nanoplastics, especially on cardiovascular damage was still largely unknown. In this regard, the evaluation of cardiovascular effects of nanoplastics was performed in zebrafish embryos. The results indicated that the no observed adverse effect level (NOAEL) of nanoplastics is 50 µg/mL. The pericardial toxicity and hemodynamic changes were assessed by Albino (melanin allele) mutant zebrafish line. Severe pericardial edema was observed in zebrafish embryos after exposure to nanoplastics. At the concentration higher than NOAEL, nanoplastics significantly decreased the cardiac output (CO) and blood flow velocity. The fluorescence images manifested that the nanoplastics could inhibit the subintestinal angiogenesis of transgenic zebrafish embryos line Tg (fli-1: EGFP), which might disturb the cardiovascular formation and development. The resulting vascular endothelial dysfunction and hypercoagulable state of circulating blood further accelerated thrombosis. Reactive oxidative stress (ROS) and systemic inflammation were also found in Wild AB and Tg (mpo: GFP) zebrafish embryos, respectively. We also found many neutrophils recruiting in the tail vein where the zebrafish embryo thrombosis occurred. Our data suggested that nanoplastics could trigger the cardiovascular toxicity in zebrafish embryos, which could provide an essential clue for the safety assessment of nanoplastics.

Ebselen-Agents for Sensing, Imaging and Labeling: Facile and Full-Featured Application in Biochemical Analysis.

Phenyl-1,2-benzoselenazol-3(2H)-one (ebselen) is a classical mimic of glutathione peroxidase (GPx). Thioredoxin interaction endows ebselen attractive biological functions, such as antioxidation and anti-infection, as well as versatile therapeutic usage. Accordingly, application of ebselen analogues in biosensing, chemical labeling, imaging analysis, disease pathology, drug development, clinical treatment, etc. have been widely developed, in which mercaptans, reactive oxygen species, reactive sulfur species, peptides, and proteins were involved. Herein, focusing on the application of ebselen-agents in biochemistry, we have made a systematic summary and comprehensive review. First, we summarized both the classical and the innovative methods for preparing ebselen-agents to present the synthetic strategies. Then we discussed the full functional applicability of ebselen analogues in three fields of biochemical analysis including the fluorescence sensing and bioimaging, derivatization for high throughput fluorescence analysis, and the labeling gents for proteomics. Finally, we discussed the current challenges and perspectives for ebselen-agents as analytical tools in biological research. By presenting the multifunctional applicability of ebselen, we hope this review could appeal researchers to design the ebselen-related biomaterials for biochemical analysis.

RhB-encapsulating silica nanoparticles modified with PEG impact the vascular endothelial function in endothelial cells and zebrafish model.

Silica nanoparticles (SiNPs) have been widely used in human health related products, such as food additives, cosmetics and even drug delivery, gene therapy or bioimaging. Recently, a first-in-human clinical trial based on polyethylene glycol (PEG)-modified SiNPs had been approved by US FDA to trace melanoma. However, as a nano-based drug delivery system, its biocompatibility and vascular toxicity are still largely unknown. Thus, we synthesized the fluorescent SiNPs to explore the biocompatibility and vascular endothelial function, and compare different biological effects caused by PEG-modified and unmodified SiNPs in cells and zebrafish model. The characterizations of SiNPs and PEG-modified SiNPs were analyzed by TEM, SEM, AFM and DLS, which exhibited relatively good stable and dispersive. Compared with SiNPs, PEG-modified SiNPs had markedly reduced the inflammatory response and vascular damage in Tg (fli-1: EGFP) and Tg (mpo: GFP) transgenic zebrafish lines, respectively. Consistent with the in vivo results, the PEG-modified SiNPs had been found to significantly decline the levels of ROS, inflammatory cytokines and mitochondrial-mediated apoptosis in vascular endothelial cells compared to SiNPs, and the ROS scavenger NAC could effectively alleviate the above adverse effects induced by nanoparticles. Our results suggested that the PEG-modified SiNPs could become more safety via increasing the biocompatibility and decreasing cellular toxicities in living organisms.

Supramolecular polymeric chemotherapy based on cucurbit[7]uril-PEG copolymer.

We develop a strategy of supramolecular polymeric chemotherapy based on a new kind of water-soluble polymer that bears cucurbit[7]uril (CB[7]) in the main-chain. To this end, we synthesized a bis-alkynyl functionalized CB[7] and polymerized it with α,ω-diazide-PEG through click reaction to form the desired CB[7] based main-chain polymer (poly-CB[7]). Anticancer drug, oxaliplatin, could be encapsulated into the cavity of poly-CB[7] to form a supramolecular polymeric complex, which displayed low cytotoxicity to normal cells. In addition, the cytotoxicity of the oxaliplatin was recovered when the complex met cancer cells that could overexpress spermine, e.g. colorectal cancer cell, through competitive replacement of oxaliplatin from CB[7] cavity by spermine. Interestingly, the cytotoxicity of the supramolecular polymeric complex to cancer cells is higher than oxaliplatin itself. The enhanced cytotoxicity should result from a combined effect by combining the release of oxaliplatin from the supramolecular polymeric complex and decrease of spermine in the micro-environment of the cancer cells, as spermine is needed for cell growth and proliferation. One more advantage of the supramolecular polymeric complex is its long circulation performance in vivo compared with the supramolecular complex between oxaliplatin and CB[7]. Therefore, this line of research may open new horizons for supramolecular polymeric chemotherapy.

Characterization of crystal structure in binary mixtures of latex globules.

Colloidal crystals formed by two types of polystyrene particles of different sizes (94 and 141 nm) at various number ratios (94:141 nm) are studied. Experiments showed that the formation time of crystals lengthens as the number ratio of the two components approaches 1:1. The dependence of the mean interparticle distance (D(0)), crystal structure and alloy structure on the number ratio of the two types of particles was studied by means of Kossel diffraction technique and reflection spectra. The results showed that as the number ratio decreased, the mean interparticle distance (D(0)) became larger. And the colloidal crystal in binary mixtures is more preferably to form the bcc structure. This study found that binary systems form the substitutional solid solution (sss)-type alloy structure in all cases except when the number ratio of two types of particles is 5:1, which results instead in the superlattice structure.