Retinal Microenvironment-Protected Rhein-GFFYE Nanofibers Attenuate Retinal Ischemia-Reperfusion Injury via Inhibiting Oxidative Stress and Regulating Microglial/Macrophage M1/M2 Polarization.

Retinal ischemia is involved in the occurrence and development of various eye diseases, including glaucoma, diabetic retinopathy, and central retinal artery occlusion. To the best of our knowledge, few studies have reported self-assembling peptide natural products for the suppression of ocular inflammation and oxidative stress. Herein, a self-assembling peptide GFFYE is designed and synthesized, which can transform the non-hydrophilicity of rhein into an amphiphilic sustained-release therapeutic agent, and rhein-based therapeutic nanofibers (abbreviated as Rh-GFFYE) are constructed for the treatment of retinal ischemia-reperfusion (RIR) injury. Rh-GFFYE significantly ameliorates oxidative stress and inflammation in an in vitro oxygen-glucose deprivation (OGD) model of retinal ischemia and a rat model of RIR injury. Rh-GFFYE also significantly enhances retinal electrophysiological recovery and exhibits good biocompatibility. Importantly, Rh-GFFYE also promotes the transition of M1-type macrophages to the M2 type, ultimately altering the pro-inflammatory microenvironment. Further investigation of the treatment mechanism indicates that Rh-GFFYE activates the PI3K/AKT/mTOR signaling pathway to reduce oxidative stress and inhibits the NF-κB and STAT3 signaling pathways to affect inflammation and macrophage polarization. In conclusion, the rhein-loaded nanoplatform alleviates RIR injury by modulating the retinal microenvironment. The findings are expected to promote the clinical application of hydrophobic natural products in RIR injury-associated eye diseases.

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.

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.

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.

Size-Dependent Cytotoxicity and Reactive Oxygen Species of Cerium Oxide Nanoparticles in Human Retinal Pigment Epithelia Cells.

PURPOSE: The use of cerium oxide nanoparticles (CeO2 NPs), a lanthanide element oxide and bivalent compound, has been growing continuously in industry and biomedicine. Due to their wide application, the potential human health problems of CeO2 NPs have attracted attention, but studies on the toxicity of this compound to human eyes are lacking. This study investigated the cytotoxicity and reactive oxygen species (ROS) of CeO2 NPs in human retinal pigment epithelial cells (ARPE-19 cells). METHODS: Using the transmission electron microscope (TEM), the size distribution and shape of CeO2 NPs were characterized. To explore the effect of CeO2 NP size on ophthalmic toxicity in vitro, three sizes (15, 30 and 45 nm) of CeO2 NPs were investigated using ATP content measurement, LDH release measurement and cell proliferation assay in ARPE-19 cells. ROS values and mitochondrial membrane potential depolarization were evaluated by H2DCF-DA staining and JC-1 staining. Morphology changes were detected using a phase-contrast microscope. RESULTS: The cytotoxicity of 15 nm CeO2 NPs was found to be the highest and hence was further explored. Treatment with 15 nm CeO2 NPs caused the morphology of ARPE-19 cells to change in a dose- and time-dependent manner. Moreover, the treatment induced excessive ROS generation and mitochondrial membrane potential depolarization. In addition, cytotoxicity was attenuated by the application of a ROS scavenger N-acetyl-L- cysteine (NAC). CONCLUSION: CeO2 NPs induced cytotoxicity in ARPE-19 cells and excessive production of ROS and decreasing mitochondrial membrane potential. The Overproduction of ROS partially contributes to CeO2 NP-induced cytotoxicity.