Enhanced Stability of α-Mangostin-Rich Extract and Selective Cytotoxicity against Cancer Cells via Encapsulation in Antioxidant Nanoparticles (AME@NanoAOX).

α-Mangostin-rich extract (AME) shows promise as a functional ingredient for cancer chemotherapy. Here, we encapsulated AME in our originally designed antioxidant nanoparticles (NanoAOX) to increase its solubility and prevent oxidative degradation (AME@NanoAOX). In this study, two types of self-assembled polymers containing nitroxide radicals were engineered. These polymers were self-assembled into nanoscale particles in aqueous media, entrapping AME (abbreviated as AME@NanoAOX(B) and AME@NanoAOX(G)). These formulations considerably improved the stability of AME against oxidative degradation and exhibited different release profiles of α-mangostin under different pH conditions. Furthermore, AME-encapsulated nanoparticles exhibited potent cytotoxicity against various cancer cell lines, including human breast cancer (MCF-7), human lung cancer (A549), human colon cancer (Caco-2), human cervical cancer (HeLa), and human liver cancer (HepG2) cell lines, with minimal cytotoxicity in normal human mammary epithelial cells (hTERT-HME1), thus providing a high selectivity index (SI). These results indicated the promising feature of AME-encapsulated antioxidant nanoparticles (AME@NanoAOX) for cancer chemotherapy.

Design of Antioxidant Nanoparticle, which Selectively Locates and Scavenges Reactive Oxygen Species in the Gastrointestinal Tract, Increasing The Running Time of Mice.

Excess reactive oxygen species (ROS) produced during strong or unfamiliar exercise cause exercise-induced gastrointestinal syndrome (EIGS), leading to poor health and decreased exercise performance. The application of conventional antioxidants can neither ameliorate EIGS nor improve exercise performance because of their rapid elimination and severe side effects on the mitochondria. Hence, a self-assembling nanoparticle-type antioxidant (RNPO ) that is selectively located in the gastrointestinal (GI) tract for an extended time after oral administration is developed. Interestingly, orally administered RNPO significantly enhances the running time until exhaustion in mice with increasing dosage, whereas conventional antioxidants (TEMPOL) tends to reduce the running time with increasing dosage. The running (control) and TEMPOL groups show severe damage in the GI tract and increased plasma lipopolysaccharide (LPS) levels after 80 min of running, resulting in fewer red blood cells (RBCs) and severe damage to the skeletal muscles and liver. However, the RNPO group is protected against GI tract damage and elevation of plasma LPS levels, similar to the nonrunning (sedentary) group, which prevents damage to the whole body, unlike in the control and TEMPOL groups. Based on these results, it is concluded that continuous scavenging of excessive intestinal ROS protects against gut damage and further improves exercise performance.

An Antioxidant Nanoparticle Enhances Exercise Performance in Rat High-intensity Running Models.

Although the adverse effects of excessively generated reactive oxygen species (ROS) on the body during aerobic exercise have been debated, there are few reports on the remarkable effects of the application of conventional antioxidants on exercise performance. The conventional antioxidants could not enhance exercise performance due to their rapid excretion from the body and serious adverse effects on the cellular respiratory system. In this study, impact of the original antioxidant self-assembling nanoparticle, redox-active nanoparticle (RNP), is investigated on the exercise performance of rats during running experiments. With an increase in the dose of the administered RNP, the all-out time of the rat running extends in a dose-dependent manner. In contrast, with an increase in the dose of the low-molecular-weight (LMW) antioxidant, the all-out running time of the rats decreases. The control group and LMW antioxidant treated group decrease in the number of red blood cells (RBCs) and increase oxidative stress after running. However, the RNP group maintains a similar RBC level and oxidative stress as that of the sedentary group. The results suggest that RNP, which shows long-blood circulation without disturbance of mitohormesis, effectively removes ROS from the bloodstream to suppresses RBC oxidative stress and damage, thus improving exercise performance.