Amphiphilic Block Copolymers Containing Benzenesulfonyl Azide Groups as Visible Light-Responsive Drug Carriers for Image-Guided Delivery.

Nanoparticles (NPs) containing light-responsive polymers and imaging agents show great promise for controlled drug delivery. However, most light-responsive NPs rely on short-wavelength excitation, resulting in poor tissue penetration and potential cytotoxicity. Moreover, excessively sensitive NPs may prematurely release drugs during storage and circulation, diminishing their efficacy and causing off-target toxicity. Herein, we report visible-light-responsive NPs composed of an amphiphilic block copolymer containing responsive 4-acrylamide benzenesulfonyl azide (ABSA) and hydrophilic N,N'-dimethylacrylamide (DMA) units. The polymer pDMA-ABSA was loaded with the chemotherapy drug dasatinib and zinc tetraphenylporphyrin (ZnTPP). ZnTPP acted as an imaging reagent and a photosensitizer to reduce ABSA upon visible light irradiation, converting hydrophobic units to hydrophilic units and disrupting NPs to trigger drug release. These NPs enabled real-time fluorescence imaging in cells and exhibited synergistic chemophotodynamic therapy against multiple cancer cell lines. Our light-responsive NP platform holds great promise for controlled drug delivery and cancer theranostics, circumventing the limitations of traditional photosensitive nanosystems.

High-Temperature Soup Foods in Plastic Packaging Are Associated with Phthalate Body Burden and Expression of Inflammatory mRNAs: A Dietary Intervention Study.

Plastic packaging material is widely used to package high-temperature soup food in China, but this combination might lead to increased exposure to phthalates. The health effects and potential biological mechanisms have not been well studied. This study aimed to examine urinary phthalate metabolites and the expression of inflammatory cytokines in the blood before, during, and after a "plastic-packaged high-temperature soup food" dietary intervention in healthy adults. The results showed that compared with those in the preintervention period, urinary creatinine-adjusted levels of monomethyl phthalate (MMP), mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MIBP), and total phthalate metabolites in the intervention period were significantly higher, with increases of 71.6, 41.8, 38.8, and 29.8% for MMP, MBP, MIBP, and the total phthalate metabolites, respectively. After intervention, the mean levels of IL-1ß, IL-4, and TNF-α mRNA increased by 19.0, 21.5, and 25.0%, respectively, while IL-6 and IFN-γ mRNA decreased by 24.2 and 32.9%, respectively, when compared with the preintervention period. We also observed that several phthalates were associated with the mRNA or protein expression of IL-8, TNF-α, and IL-10. Therefore, consumption of plastic-packaged high-temperature soup food was linked to increased phthalate exposure and might result in significant changes in mRNA expression of several inflammatory cytokines.

Structural homeostasis and controlled release for anthocyanin in oral film via sulfated polysaccharides complexation.

Oral film is a novel functional carrier, which can provide a new pathway for the efficient absorption of anthocyanin. However, anthocyanin homeostasis in oral film is a prerequisite for achieving efficient absorption and utilization of anthocyanin. Herein, three sulfated polysaccharides, including chondroitin sulfate (CS), fucoidin (FU) and λ-carrageenan (λ-CG), were complexed with blueberry anthocyanin (BA) to prepare oral film formulations using hydroxypropyl methylcellulose (HPMC) as a film-forming matrix. The addition of three sulfated polysaccharides improved the stability of BA in content and color, which were associated with interactions between BA and polysaccharides. The BA retention rate of CS-BA/HPMC system increased 5.5-fold after 8 d of light-accelerated storage compared with the control group, showing the best homeostasis effect. CS and λ-CG enhanced the elongation at break and prolonged disintegration time of oral films. The addition of FU made the oral film denser and smoother, and had the highest BA release (75.72 %) in the simulated oral cavity system. In addition, the oral films of three sulfated polysaccharides complexed with BA showed superior antioxidant capacity. The present study provides new insights into the application of anthocyanin in film formulation carriers.

Unraveling the effects and mechanisms of microplastics on anaerobic fermentation: Exploring microbial communities and metabolic pathways.

To investigate the effects of microplastics (MPs) on hydrolysis, acidification and microbial characteristics during waste activated sludge (WAS) anaerobic fermentation process, five different kinds of MPs were added into the WAS fermentation system and results indicated that, compared to the control group, the addition of polyvinyl chloride (PVC)-MPs exhibited the least inhibition on volatile fatty acids (VFAs), reducing them by 13.49 %. Conversely, polyethylene (PE)-MPs resulted in the greatest inhibition, with a reduction of 29.57 %. MPs, while accelerated the dissolution of WAS that evidenced by an increase of lactate dehydrogenase (LDH) release, concurrently inhibited the activities of relevant hydrolytic enzymes (α-Glucosidase, protease). For microbial mechanisms, MPs addition affected the proliferation of key microorganisms (norank_f_Bacteroidetes_vadinHA17, Ottowia, and Propioniclava) and reduced the abundance of genes associated with hydrolysis and acidification (pfkb, gpmI, ilvE, and aces). Additionally, MPs decreased the levels of key hydrolytic and acidogenic enzymes to inhibit hydrolysis and acidification processes. This research provides a basis for understanding and unveils impact mechanisms of the impact of MPs on sludge anaerobic fermentation.

Ultrasound-responsive glycopolymer micelles for targeted dual drug delivery in cancer therapy.

Controlled drug release of nanoparticles was achieved by irreversibly disrupting polymer micelles through high-intensity focused ultrasound (HIFU) induction. An ultrasound-responsive block copolymer was synthesized, comprising an end-functional Eosin Y fluorophore, 2-tetrahydropyranyl acrylate (THPA), and acrylate mannose (MAN). The block copolymer was then self-assembled to produce micelles. The chemotherapy drug dasatinib (DAS) and the sonodynamic therapy agent methylene blue (MB) were encapsulated by the self-assembly of the block copolymer. This targeted nanoparticle enables sonodynamic therapy through high-intensity focused ultrasound while triggering nanoparticle disassembly for controlled drug release. The ultrasound-mediated, non-invasive strategy provides external spatiotemporal control for targeted tumour treatment.

Physiological analysis and transcriptome profiling reveals the impact of microplastic on melon (Cucumis melo L.) seed germination and seedling growth.

The wide application of agricultural plastics leads to microplastic (MP) accumulation in the soil and inevitably result in MP pollution. Melon is an economically important horticultural crop that is widely cultivated with plastic film mulching. However, the impact of MP pollution on plant growth remains largely unclear. Here we reported the morphological, physiological, biochemical responses and transcriptome re-programing of melon responses to MP on seed germination and seedling growth. Polyvinyl chloride particles were added to potting mix to simulate MP exposure environment (MEE). The results showed that low and medium concentrations (1-4 g kg-1) of MEE had a significant adverse effect on seed germination and seedling growth. In both cases, the germination potential was decreased, young root forks increased, and tips decreased; and the dry weight of seedlings, the total length, surface area, forks and tips of root were also decreased. However, the root activity was increased. The concentration of MEE to give the best parameters was at 2 g kg-1. Catalase enzymatic activity and reactive oxygen species (ROS) in roots were decreased continuously with increased MEE concentrations. The peak values of peroxidase activity, O2.- content and generation rate, ROS enrichment and malondialdehyde content all reached the highest at 2 g kg-1. MEE also increased the proline content and decreased the contents of ascorbic acid, soluble sugar and soluble protein in these seedlings. Medium and high concentrations of MEE (4-8 g kg-1) also increased the chlorophyll b content. Low concentrations MEE (1-2 g kg-1) inhibited actual photochemical efficiency of photosystem II and photochemical quenching, two key chlorophyll fluorescence parameters. Transcriptome analysis showed that the differentially expressed genes caused by the MEE were mainly belonged to defense response, signal transduction, hormone metabolism, plant-pathogen interaction, and phenylpropanoid biosynthesis. The results of this study will help to understand the ecotoxicological effects of MEE on melons and provide data for ecological risk assessment of Cucurbitaceae vegetable cultivation.

A targeted and redox/pH-responsive chitosan oligosaccharide derivatives based nanohybrids for overcoming multidrug resistance of breast cancer cells.

A novel folic acid mediated chitosan oligosaccharide-grafted disulfide-containing polyethylenimine copolymer-based silica nanohybrids were fabricated for co-delivering paclitaxel and P-shRNA. These nanoparticles could efficiently protect P-shRNA against degradation, and exhibited well redox-responsive P-shRNA release and pH-responsive drug release behaviors. Folic acid as the targeting head, could improve cellular uptake of nanoparticles by multidrug-resistant breast cancer cells. Moreover, these nanoparticles showed excellent delivery P-shRNA into cells and displayed high gene silencing efficiency at the targeted mRNAs to downregulate the expression of P-gp which induced up to 63% decrease. Finally, nanoparticles could completely reverse the resistance of breast cancer cells to paclitaxel and the resistance reversion index was 50.59. These results suggested that our nanoparticles could efficiently co-deliver paclitaxel and P-shRNA into cancer cells to exert its synergistic antitumor effect, and opened up a new avenue for overcoming multidrug resistance.

N-Halamine polymer from bipolymer to amphiphilic terpolymer with enhancement in antibacterial activity.

A novel N-halamine terpolymer, i.e., P(ADMH-MMA-HEMA)-Cl, with high antibacterial efficacies were fabricated via a free-radical copolymerization of 3-allyl-5,5-dimethylhydantoin(ADMH), methyl methacrylate(MMA), and hydroxyethyl methacrylate (HEMA), followed by a chlorination treatment using sodium hypochlorite as chlorinating agent. A controllable synthesis of P(ADMH-MMA-HEMA)-Cl was achieved by tuning chlorination conditions, such as chlorination temperature, reactant concentration, chlorination time, etc. A series of antibacterial assays were conducted, and the as-prepared products P(ADMH-MMA-HEMA)-Cl showed good killing capabilities against both Gram-positive and Gram negative bacteria. Remarkably, compared to N-halamine biopolymer counterparts, e.g., P(ADMH-HEMA)-Cl and P(ADMH-MMA)-Cl, and the as-prepared N-halamine terpolymer P(ADMH-MMA-HEMA)-Cl presented the enhancement in antibacterial efficiency toward pathogens. It is believed that this approach offers great potential to be utilized in various fields where antibacterial properties are highly required.

Recent Advances in Application of Poly-Epsilon-Caprolactone and its Derivative Copolymers for Controlled Release of Anti-Tumor Drugs.

BACKGROUND: Due to their excellent biocompatibility and biodegradability, poly-epsiloncaprolactone and its derivative copolymers have been extensively studied as drug carriers in pharmaceutical and medical fields, especially for controlled release of anti-tumor drugs. Poly-epsiloncaprolactone based drug delivery systems lead to major advantages including uniform drug distribution, long term of degradation and drug release process, non-toxic in nature and cyto-compatible with body tissues. Approved by US Food and Drug Administration, poly-epsilon-caprolactone provides a promising platform for design and fabrication of anti-tumor drug delivery systems with controllable drug release behaviors. METHODS: This mini-review focused on the recent progress in application of poly-epsiloncaprolactone based materials for controlled release of cancer therapy drugs. A careful search was performed on web of science, mainly focused on the related papers published from 2013 to 2016. CONCLUSION: Recent advances in applying poly-epsilon-caprolactone for controlled delivery and targeting release of chemical anti-tumor drugs were summarized in this mini-review. Benefited from the efforts of scientists all over the world, various chemotherapeutic drug delivery systems based on different formulations of poly-epsilon-caprolactone related materials have been evaluated. It has been widely recognized that the introduction of of poly-epsilon-caprolactone components into drug delivery systems would increase drug loading capacity, decrease leakage, prolong releasing period and result in controllable releasing rate. Especially with the development of environment-responsive delivery systems (pH-, thermo-, magnetic field- and light-responsive drug carriers), enhanced tumor cell targeting potential, as well as decreased systemic toxicity would be realized.

Stability and phase behavior of acrylamide-based emulsions before and after polymerization.

The stability and phase behavior of acrylamide-based emulsions, prepared with surfactants consisting of lipophilic Span80 and hydrophilic OP10, before or after polymerization were investigated. The research results indicated that the phase separation behavior of the W/O-type emulsions is related to the toluene/water ratio. When the water volume fraction was larger, the phase separation mechanism was mainly a penetration of aqueous molecules from the dispersed-phase droplets. When the water volume fraction was smaller, the phase separation mechanism was mainly a sedimentation of the separated aqueous droplets. At a fixed toluene/water ratio, the emulsion stability and the emulsion type are related not only to the ratio of the two surfactants but also to the acrylamide concentration, and the effect of increasing acrylamide concentration on the character of the emulsions is similar to that of increasing OP10 mass fraction (increasing HLB value), which determines the corresponding relationship between acrylamide concentration and HLB value in the most stable emulsion system. To obtain the most stable emulsion at a fixed acrylamide concentration, the emulsion with higher acrylamide concentration needs a lower HLB value for the emulsion systems.

Simulated force-induced unfolding of alpha-helices: dependence of stretching stability on primary sequence.

Some of the principles that determine a protein's native fold can be probed with techniques for single-molecule manipulation. Yet, understanding the effects of an external force at atomic level still requires computer simulations. Here, we employ a novel protocol for steered molecular dynamics that allows for internal energy redistribution (and possibly, re-equilibration) while the molecule is subject to a mechanical perturbation. The approach is used to study how the stretching of alpha-helices is qualitatively affected by variations in primary sequence. Despite the simplifications introduces, our results indicate a trend whereby different amino acids can increase the resistance to mechanical unfolding depending on side chain polarity and the dynamics of side-chain internal torsions. Whereas the cooperative transition from alpha-helix to 310-helix and to a rod-like conformer prevails when stretching many sequences, we also find that the onset of the unfolding can be delayed by a range of alternative pathways which include events of helical refolding or long-lived intermediates with partial helical content.

Gradients of substrate-bound laminin orient axonal specification of neurons.

Little is known about the influence of substrate-bound gradients on neuronal development, since it has been difficult to fabricate gradients over the distances typically required for biological studies (a few hundred micrometers). This article demonstrates a generally applicable technique for the fabrication of substrate-bound gradients of proteins with complex shapes, using laminar flows in microchannels. Gradients that range from pure laminin to pure BSA were formed in solution by using a network of microchannels, and these proteins were allowed to adsorb onto a homogeneous layer of poly-l-lysine. Rat hippocampal neurons were cultivated on these substrate-bound gradients. Analysis of optical images of these neurons showed that axon specification is oriented in the direction of increasing surface density of laminin. Linear gradients in laminin adsorbed from a gradient in solution having a slope of nabla [laminin] > about 0.06 microg (ml.microm)(-1) (defined by dividing the change of concentration of laminin in solution over the distance of the gradient) orient axon specification, whereas those with nabla [laminin] < about 0.06 microg (ml.microm)(-1) have no effect.