Targeted paclitaxel prodrug nanoassemblies to improve therapeutic effects for liver cancer.

Prodrug nanoassemblies fabricated by anticancer drug conjugates exhibited more advantages in controlled drug release and bioavailability and favorable antitumor efficacy. In this paper, lactobionic acid (LA) was connected with polyethylene glycol through amido linkages, and paclitaxel was joined with polyethylene glycol by means of ester bonds to form the prodrug copolymer LA-PEG-PTX. Then, LA-PEG-PTX was automatically assembled into LA-PEG-PTX nanoparticles (LPP NPs) by dialysis. The LPP NPs had a relatively uniform size of approximately 200 nm, a negative potential (-13.68 mV), and a spherical shape under TEM. The drug loading of LPP NPs was 3.91%, which was measured by HPLC. The in vitro release profile of LPP NPs exhibited a sustained release feature. The results of the pharmacokinetic test in rats showed that LPP NPs had higher T1/2 and AUC values than the control group (free PTX) and a prolonged in vivo circulation time, thus increasing the bioavailability of PTX. Remarkably, the LPP NPs were absorbed into HepG2 cells after galactose-directed internalization and enhanced cytotoxicity. Consequently, LPP NPs displayed notable antitumor activity in Kunming mice with H22 hepatocellular carcinoma. Collectively, these findings suggested that paclitaxel prodrug-based self-assembled nanoparticles were a promising alternative for improving the bioavailability and antitumor effect of PTX.

Simultaneously enhanced treatment efficiency of simulated hypersaline azo dye wastewater and membrane antifouling by a novel static magnetic field membrane bioreactor (SMFMBR).

Operation performance and membrane fouling of a novel static magnetic field membrane bioreactor (SMFMBR) for treatment of hypersaline azo dye wastewater was investigated. The results showed that SMFMBRs possessed higher efficiency of dye decolorization, COD removal and detoxification than the control MBR without SMF. The (3#) SMFMBR equipped with 305.0 mT (the highest intensity) SMF displayed the best treatment performance among all the four reactors (named as 0#-3#, equipped with SMFs of 0 mT, 95.0 mT, 206.3 mT and 305.0 mT, respectively). Potentially effective microbes belonging to Rhodanobacter, Saccharibacteria genera incertae sedis, Defluviimonas, Cellulomonas, Cutaneotrichosporon, Candida and Pichia were enriched in three SMFMBRs, in both of suspended sludge and bio-cakes. The relative abundance of Candida and Pichia in suspended sludge of 3# SMFMBR was the highest among all the four reactors, suggesting their successful colonization and potentially persistent effect of bioaugmentation. On the other hand, SMF of higher intensity effectively mitigated membrane fouling. Less production of soluble microbial products (SMP) and extracellular polymeric substances (EPS), lower protein/polysaccharide (PN/PS) ratio in SMP and EPS, looser structure of bio-cakes on membrane surface, as well as lower relative abundance of potential fouling causing microbes (mainly bacteria) in microbial communities were determined in 3# SMFMBR than the other three groups.

Self-Propelled Nanomotors with an Alloyed Engine for Emergency Rescue of Traumatic Brain Injury.

In severe traumatic brain injury (sTBI), acute oxidative stress and inflammatory cascades rapidly spread to cause irreversible brain damage and low survival rate within minutes. Therefore, developing a feasible solution for the quick-treatment of life-threatening emergency is urgently demanded to earn time for hospital treatment. Herein, Janus catalysis-driven nanomotors (JCNs) are carefully constructed via plasma-induced alloying technology and sputtering-caused half-coating strategy. The theoretical calculation and experiment results indicate that the heteroatom-doping alloyed engine endows JCNs with much higher catalytic activity for removing reactive oxygen species and reactive nitrogen species than common Pt-based engines. When JCNs are dropped to the surface of the ruptured skull, they can effectively catalyze endogenous hydrogen peroxide, which induces movement as fuels to promote JCNs to deep brain lesions for further nanocatalyst-mediated cascade-blocking therapy. The results demonstrate that the JCNs successfully block the inflammatory cascades, thereby reversing multiple behavioral defects and dramatically declining the mortality of sTBI mice. This work provides a revolutionary nanomotor-based strategy to sense brain injury and scavenge oxidative stress. Meanwhile, the JCNs provide a feasible strategy to adapt various first-aid scenarios due to their self-propelled movement combined with highly multienzyme-like catalytic activity, exhibiting tremendous therapeutic potential to help people for emergency pretreatment.

Dietary polystyrene nanoplastics exposure alters liver lipid metabolism and muscle nutritional quality in carnivorous marine fish large yellow croaker (Larimichthys crocea).

Nanoplastics (NPs) cause various adverse effects on marine fish. However, effects of dietary NPs exposure on liver lipid metabolism and muscle nutritional quality of carnivorous marine fish are not fully understood. In this study, a 21-day feeding test was conducted to simulate the food chain transfer of polystyrene nanoplastics (PS NPs) and then evaluate effects of different dietary PS NPs levels on the survival, growth performance, liver lipid metabolism, and muscle nutritional quality of large yellow croaker Larimichthys crocea. Results indicated that the survival and growth of large yellow croaker decreased with the increase of PS NPs levels. Moreover, PS NPs induced excessive liver lipid accumulation by down-regulating the expression of lipolysis-related genes and inhibiting the AMPK-PPARα signaling pathway. In vitro, PS NPs could be accumulated in hepatocytes, reduce cell viability, and disrupt lipid metabolism of hepatocytes. Also, we found for the first time that PS NPs altered fatty acid composition and texture of fish muscle by enhancing oxidative stress and disrupting lipid metabolism. Overall, this study indicated that PS NPs induced liver lipid deposition by inhibiting lipolysis, and demonstrated that PS NPs altered the nutritional quality of fish, which might cause potential health effects for human consumers.

Bactericidal Dendritic Polycation Cloaked with Stealth Material via Lipase-Sensitive Intersegment Acquires Neutral Surface Charge without Losing Membrane-Disruptive Activity.

Net cationicity of membrane-disruptive antimicrobials is necessary for their activity but may elicit immune attack when administered intravenously. By cloaking a dendritic polycation (G2) with poly(caprolactone-b-ethylene glycol) (PCL-b-PEG), we obtain a nanoparticle antimicrobial, G2-g-(PCL-b-PEG), which exhibits neutral surface charge but kills >99.9% of inoculated bacterial cells at ≤8 µg/mL. The observed activity may be attributed PCL's responsive degradation by bacterial lipase and the consequent exposure of the membrane-disruptive, bactericidal G2 core. Moreover, G2-g-(PCL-b-PEG) exhibits good colloidal stability in the presence of serum and insignificant hemolytic toxicity even at ≥2048 µg/mL. suggesting good blood compatibility required for intravenous administration.