Chenodeoxycholic Acid-Modified Polyethyleneimine Nano-Composites Deliver Low-Density Lipoprotein Receptor Genes for Lipid-Lowering Therapy by Targeting the Liver.

Lipid-lowering drugs, especially statins, are extensively utilized in clinical settings for the prevention of hyperlipidemia. Nevertheless, prolonged usage of current lipid-lowering medications is associated with significant adverse reactions. Therefore, it is imperative to develop novel therapeutic agents for lipid-lowering therapy. In this study, a chenodeoxycholic acid and lactobionic acid double-modified polyethyleneimine (PDL) nanocomposite as a gene delivery vehicle for lipid-lowering therapy by targeting the liver, are synthesized. Results from the in vitro experiments demonstrate that PDL exhibits superior transfection efficiency compared to polyethyleneimine in alpha mouse liver 12 (AML12) cells and effectively carries plasmids. Moreover, PDL can be internalized by AML12 cells and rapidly escape lysosomal entrapment. Intravenous administration of cyanine5.5 (Cy5.5)-conjugated PDL nanocomposites reveals their preferential accumulation in the liver compared to polyethyleneimine counterparts. Systemic delivery of low-density lipoprotein receptor plasmid-loaded PDL nanocomposites into mice leads to reduced levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TC) in the bloodstream without any observed adverse effects on mouse health or well-being. Collectively, these findings suggest that low-density lipoprotein receptor plasmid-loaded PDL nanocomposites hold promise as potential therapeutics for lipid-lowering therapy.

Ferritin-Nanocaged ATP Traverses the Blood-Testis Barrier and Enhances Sperm Motility in an Asthenozoospermia Model.

Sperm motility can be enhanced by adding ATP exogenously during in vitro fertilization. However, administering exogenous ATP to the testis to improve sperm motility for in vivo asthenozoospermia treatment has not been investigated yet. Inspired by the recent advances in nanomedicine, we investigated whether the capability of drug delivery nanocarriers to traverse the blood-testis barrier (BTB) can facilitate ATP-dependent asthenozoospermia treatment. We found that the human H-ferritin (HFn) nanocarrier possesses the capability to traverse the BTB and specifically targets the head of elongated sperm cells. Specifically, the HFn nanocarrier traversed the BTB and accumulated in the sperm heads by binding with the HFn receptor (HFR), whose expression was relatively low in Sertoli cells but high in sperm heads. In a gossypol-induced mouse asthenozoospermia model, the administration of an ATP-loaded HFn nanocage through a tail vein injection significantly improved sperm motility. Moreover, the HFn nanocarrier was not toxic to mice in the short (1d) and long terms (30d, 90d) nor did it affect their reproductive health. Thus, the ATP-loaded HFn nanocarrier can potentially serve as a drug-delivery system for treating asthenozoospermia.

Antibacterial effects of nano-decoction iron polysulfide in epididymitis and the systematic evaluation of its toxicity on the reproductive health of male mice.

Ferrous iron and polysulfide (Fe(II)Sn aq) is a nano-decoction. It is usually prepared from the suspension of iron sulfide nanomaterial, using autoclave and centrifugation. A previous study conducted in our laboratory revealed that Fe(II)Sn aq was highly antibacterial, and it could efficiently kill more than 90% population of Escherichia coli and Staphylococcus aureus, within 5 min of the treatment. Our study reported that the intravenous administration of Fe(II)Sn aq provided effective treatment against epididymis infection, caused by S. aureus. The results of the study further highlighted its potential for clinical application. However, its effects on the reproductive system and overall health of mammals have not been investigated earlier. The present study assessed the impacts of Fe(II)Sn aq on reproductive health and other aspects of male mice. Briefly, male mice were exposed to Fe(II)Sn aq, either intravenously at the dose of 0.7 mM, 1.4 mM, and 2.8 mM of Fe2+or orally at the dose of 1.4 mM, 2.8 mM, and 5.6 mM of Fe2+. Following this, body weight, organs index, quality of sperm, blood biochemical markers, histopathology of organs, oxidative stress and apoptosis were evaluated, after 1 day and 30 days of exposure. In addition, male reproductivity was evaluated in terms of mating with female mice, and the body weight of the resulting offspring was recorded. Our results showed that the mice processed with Fe(II)Sn aq exhibited normal physiological status and reproductive capability. The present study illustrated the short- and long-term influences of Fe(II)Sn aq on the fertility of male mice for the first time. The findings of the study provided a valuable reference for the application of Fe(II)Sn aq, particularly in terms of reproductive safety.