ROS generation and p-38 activation contribute to montmorillonite-induced corneal toxicity in vitro and in vivo.

BACKGROUND: Montmorillonite (Mt) and its derivatives are now widely used in industrial and biomedical fields. Therefore, safety assessments of these materials are critical to protect human health after exposure; however, studies on the ocular toxicity of Mt are lacking. In particular, varying physicochemical characteristics of Mt may greatly alter their toxicological potential. To explore the effects of such characteristics on the eyes, five types of Mt were investigated in vitro and in vivo for the first time, and their underlying mechanisms studied. RESULTS: The different types of Mt caused cytotoxicity in human HCEC-B4G12 corneal cells based on analyses of ATP content, lactate dehydrogenase (LDH) leakage, cell morphology, and the distribution of Mt in cells. Among the five Mt types, Na-Mt exhibited the highest cytotoxicity. Notably, Na-Mt and chitosan-modified acidic Na-Mt (C-H-Na-Mt) induced ocular toxicity in vivo, as demonstrated by increases corneal injury area and the number of apoptotic cells. Na-Mt and C-H-Na-Mt also induced reactive oxygen species (ROS) generation in vitro and in vivo, as indicated by 2',7'-dichlorofluorescin diacetate and dihydroethidium staining. In addition, Na-Mt activated the mitogen-activated protein kinase signaling pathway. The pretreatment of HCEC-B4G12 cells with N-acetylcysteine, an ROS scavenger, attenuated the Na-Mt-induced cytotoxicity and suppressed p38 activation, while inhibiting p38 activation with a p38-specific inhibitor decreased Na-Mt-induced cytotoxicity. CONCLUSIONS: The results indicate that Mt induces corneal toxicity in vitro and in vivo. The physicochemical properties of Mt greatly affect its toxicological potential. Furthermore, ROS generation and p38 activation contribute at least in part to Na-Mt-induced toxicity.

Nanoparticles loaded with pharmacologically active plant-derived natural products: Biomedical applications and toxicity.

Pharmacologically active natural products have played a significant role in the history of drug development. They have acted as sources of therapeutic drugs for various diseases such as cancer and infectious diseases. However, most natural products suffer from poor water solubility and low bioavailability, limiting their clinical applications. The rapid development of nanotechnology has opened up new directions for applying natural products and numerous studies have explored the biomedical applications of nanomaterials loaded with natural products. This review covers the recent research on applying plant-derived natural products (PDNPs) nanomaterials, including nanomedicines loaded with flavonoids, non-flavonoid polyphenols, alkaloids, and quinones, especially their use in treating various diseases. Furthermore, some drugs derived from natural products can be toxic to the body, so the toxicity of them is discussed. This comprehensive review includes fundamental discoveries and exploratory advances in natural product-loaded nanomaterials that may be helpful for future clinical development.

Retinal cell-targeted liposomal ginsenoside Rg3 attenuates retinal ischemia-reperfusion injury via alleviating oxidative stress and promoting microglia/macrophage M2 polarization.

Retinal ischemia-reperfusion (RIR) injury remains a major challenge that is detrimental to retinal cell survival in a variety of ocular diseases. However, current clinical treatments focus on a single pathological mechanism, making them unable to provide comprehensive retinal protection. A variety of natural products including ginsenoside Rg3 (Rg3) exhibit potent antioxidant and anti-inflammatory activities. Unfortunately, the hydrophobicity of Rg3 and the presence of various intraocular barriers limit its effective application in clinical settings. Hyaluronic acid (HA)- specifically binds to cell surface receptors, CD44, which is widely expressed in retinal pigment epithelial cells and M1-type macrophage. Here, we developed HA-decorated liposomes loaded with Rg3, termed Rg3@HA-Lips, to protect against retinal damage caused by RIR injury. Treatment with Rg3@HA-Lips significantly inhibited the oxidative stress induced by RIR injury. In addition, Rg3@HA-Lips promoted the transition of M1-type macrophage to the M2 type, ultimately reversing the pro-inflammatory microenvironment. The mechanism of Rg3@HA-Lips was further investigated and found that they can regulateSIRT/FOXO3a, NF-κB and STAT3 signaling pathways. Together with as well demonstrated good safety profiles, this CD44-targeted platform loaded with a natural product alleviates RIR injury by modulating the retinal microenvironment and present a potential clinical treatment strategy.

Silica nanoparticles: Biomedical applications and toxicity.

Silica nanoparticles (SiNPs) are composed of silicon dioxide, the most abundant compound on Earth, and are used widely in many applications including the food industry, synthetic processes, medical diagnosis, and drug delivery due to their controllable particle size, large surface area, and great biocompatibility. Building on basic synthetic methods, convenient and economical strategies have been developed for the synthesis of SiNPs. Numerous studies have assessed the biomedical applications of SiNPs, including the surface and structural modification of SiNPs to target various cancers and diagnose diseases. However, studies on the in vitro and in vivo toxicity of SiNPs remain in the exploratory stage, and the toxicity mechanisms of SiNPs are poorly understood. This review covers recent studies on the biomedical applications of SiNPs, including their uses in drug delivery systems to diagnose and treat various diseases in the human body. SiNP toxicity is discussed in terms of the different systems of the human body and the individual organs in those systems. This comprehensive review includes both fundamental discoveries and exploratory progress in SiNP research that may lead to practical developments in the future.