Docetaxel liposomes for lung targeted delivery: development and evaluation.

Docetaxel (DTX) is an artificial semi-synthetic second-generation taxane anti-tumor drug, which is suitable for the treatment of various cancers such as lung cancer. The route of administration of DTX formulations has been extended to oral, intravenous, and rectal, with few studies on pulmonary administration being reported. Here, we had developed DTX liposomes (DTX-lips) for pulmonary inhalation administration. The particle size of the preparation was 125 nm, the encapsulation efficiency was 94.4 ± 0.14%, and the drug loading capacity was 1.26 ± 0.01%. It had good stability. The fine particle fraction with aerodynamic diameter less than 6.4 µm accounts for 64.63 ± 0.12%, showed excellent aerosolization performance. DTX-lips were slow to release in simulated lung fluid. The fluorescence distribution experimented in mice and tissues showed that the fluorescence of the inhaled liposome group was mainly distributed in the lung, and the retention time was significantly prolonged as compared with those of the other two groups. No significant fluorescence was observed in other tissues, which was conducive to the full effect of the drug in the lung tissue. DTX-lips had no damage to respiratory system and whole body. These results indicated that the inhaled DTX-lips had good lung targeting, reduced accumulation in other organs, and improved the safety and effectiveness of the drug.

Dual-Modality Imaging with a Zwitterionic Fluorescent Probe for Reversible Monitoring of Mitochondrial Membrane Potential Dynamics.

Traditional fluorescence intensity-based probes face challenges in accurately measuring mitochondrial membrane potential (MMP) due to intramolecular fluorescence quenching. In this work, we introduce a novel approach by incorporating quenching moieties within the zwitterionic probe to eliminate self-quenching interference, thus, enabling real-time and precise visualization of reversible MMP changes. We synthesized a zwitterionic fluorescent probe consisting of silicon-rhodamine (SiR) that was hydroxyl-substituted on the bay position of perylene diimides (PDIs) connected via a polyethylene glycol (PEG) linker. The lipophilic cationic SiR facilitates the entry of the PDI into the mitochondria, where the alkaline pH environment (pH = 8.0) ionizes the hydroxyl to a negatively charged species, affecting the quenching efficiency of SiR depending on the distance between the PDI and SiR moieties regulated by the MMP. The rigid aromatic ring of the PDI and strong hydrophobic interactions with the lipid bilayer, along with the inhibitory effect of the negatively charged hydroxyl on internalization, ensure the retention of PDI within the mitochondria. As the MMP decreases, SiR shifts outward, reducing quenching by phenolic anions and restoring fluorescence. Conversely, as the MMP increases, SiR moves inward, intensifying quenching by phenolic ions and reducing fluorescence, enabling reversible visualization monitoring of the MMP. This strategy overcomes the limitations of traditional intensity-based probes, providing a new avenue for reversible monitoring of the MMP.

Lipid production from corn straw by cellobiohydrolase and delta-6 desaturase engineered Mucor circinelloides strains under solid state fermentation.

Previously, we constructed engineered M. circinelloides strains that can not only utilize cellulose, but also increase the yield of γ-linolenic acid (GLA). In the present study, an in-depth analysis of lipid accumulation by engineered M. circinelloides strains using corn straw was to be explored. When a two-stage temperature control strategy was adopted with adding 1.5% cellulase and 15% inoculum, the engineered strains led to increases in the lipid yield (up to 1.56 g per 100 g dry medium) and GLA yield (up to 274 mg per 100 g dry medium) of 1.8- and 2.3-fold, respectively, compared with the control strain. This study proved the engineered M. circinelloides strains, especially for Mc-C2PD6, possess advantages in using corn straw to produce GLA. This work provided a reference for transformation from agricultural cellulosic waste to functional lipid in one step, which might play a positive role in promoting the sustainable development of biological industry.

Effects of polystyrene nanoplastic gestational exposure on mice.

Airborne plastic particles have received increasing attention due to their ubiquity in the atmosphere and potential human health risks. Previous studies have demonstrated that early-life exposure to environmental toxicants is associated with abnormal metabolic function. However, the impact of exposure to polystyrene nanoplastics (PSNPs) through inhalation on the development of non-alcoholic fatty liver disease (NAFLD) in mothers and offspring remains unknown. In the present study, mice were gestationally exposed to PSNPs at different doses (0, 1, 5, and 25 µg µl-1) through inhalation to investigate health hazards to the dam at weaning and to adult offspring. Gestational exposure to PSNPs at high doses significantly induced hepatic steatosis in the dam and upregulated genes involved in de novo lipogenesis, fatty acids (FAs) uptake, and triacylglycerol (TG) synthesis in the monoacylglycerol acyltransferase pathway. Gestational exposure to high doses of PSNPs led to hepatic steatosis in adult female offspring but not male offspring, and expression levels of genes related to FAs uptake and TG synthesis in the glycerol 3-phosphate pathway were significantly elevated. Collectively, our data demonstrate that gestational exposure to airborne PSNPs induced different development processes of NAFLD in the dam and offspring, providing vital data about plastic particulate toxicology.

Ferroptosis Is Involved in Sex-Specific Small Intestinal Toxicity in the Offspring of Adult Mice Exposed to Polystyrene Nanoplastics during Pregnancy.

Nanoplastics are common contaminants in the living environment. Thus far, no investigations have focused on small intestinal injury in the offspring of adult mice that were exposed to nanoplastics through the respiratory system during pregnancy. Here, we evaluated potential intestinal injury in the offspring of adult mice that were subjected to maternal 80 nm polystyrene nanoparticle (PS-NP) exposure during gestation. PS-NP exposure significantly reduced the birth weight of female mice compared with male mice. However, the adult body weights of the female and male offspring were substantially greater in the PS-NP-exposed groups. Additionally, we found that exposure to PS-NPs during pregnancy caused histological changes in the small intestines of both female and male offspring. Mechanistic analysis revealed upregulation of reactive oxygen species in the small intestines, as indicated by changes in the levels of superoxide dismutase (SOD) and malondialdehyde (MDA). Furthermore, exposure to PS-NPs led to downregulation of GPx4, FTH1, and FTL protein levels, indicating initiation of ferroptosis. Notably, the changes in mRNA expression levels of GPx4, FTH1, and FTL differed between female and male offspring. Although all phenotypes failed to demonstrate classic dose-dependent effects, the data imply that small intestinal toxicity is greater in female offspring than in male offspring. Our results suggest that PS-NP exposure during pregnancy causes sex-specific small intestinal toxicity, which might contribute to reactive oxygen species activation and subsequent ferroptosis. Overall, this study showed toxic effects in offspring after PS-NP exposure during pregnancy.