H2O2-responsive antioxidant polymeric nanoparticles as therapeutic agents for peripheral arterial disease.

Peripheral artery disease (PAD) is a common circulatory disorder in which narrowed arteries limit blood flow to the lower extremity and affect millions of people worldwide. Therapeutic angiogenesis has emerged as a promising strategy to treat PAD patients because surgical intervention has been showing limited success. Leg muscles of PAD patients have significantly high level of ROS (reactive oxygen species) and the increased production of ROS is a key mechanism of initiation and progression of PAD. We have recently developed H2O2-responsive polymer PVAX, which is designed to rapidly scavenge H2O2 and release vanillyl alcohol with antioxidant and anti-inflammatory activity. In this study, we investigated the therapeutic efficacy of PVAX nanoparticles for PAD using a cell culture model and a mouse model of hindlimb ischemia. PVAX nanoparticles significantly enhanced the expression of angiogenic inducers such as vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule (PECAM)-1 in human umbilical vein endothelial cells (HUVEC). PVAX nanoparticles promoted revascularization and restoration of blood perfusion into ischemic tissues by upregulating angiogenic VEGF and PECAM-1. This work demonstrates that H2O2-responsive PVAX nanoparticles facilitate therapeutic angiogenesis and hold tremendous translational potential as therapeutic systems for ischemic diseases such as PAD.

H2O2-triggered bubble generating antioxidant polymeric nanoparticles as ischemia/reperfusion targeted nanotheranostics.

Overproduction of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) leads to oxidative stress, causing inflammation and cellular damages and death. H2O2 is one of the most stable and abundant ROS and H2O2-mediated oxidative stress is considered as a key mediator of cellular and tissue damages during ischemia/reperfusion (I/R) injury. Therefore, H2O2 could hold tremendous potential as a diagnostic biomarker and therapeutic target for oxidative stress-associated inflammatory conditions such as I/R injury. Here, we report a novel nanotheranostic agent that can express ultrasound imaging and simultaneous therapeutic effects for hepatic I/R treatment, which is based on H2O2-triggered CO2-generating antioxidant poly(vanillin oxalate) (PVO). PVO nanoparticles generate CO2 through H2O2-triggered oxidation of peroxalate esters and release vanillin, which exerts antioxidant and anti-inflammatory activities. PVO nanoparticles intravenously administrated remarkably enhanced the ultrasound signal in the site of hepatic I/R injury and also effectively suppressed the liver damages by inhibiting inflammation and apoptosis. To our best understanding, H2O2-responsive PVO is the first platform which generates bubbles to serve as ultrasound contrast agents and also exerts therapeutic activities. We therefore anticipate that H2O2-triggered bubble-generating antioxidant PVO nanoparticles have great potential for ultrasound imaging and therapy of H2O2-associated diseases.

Human anisakiasis: Diversity in antibody response profiles to the changing antigens in larval excretions/secretions.

Anisakiasis is an infectious parasitic disease contracted by eating third stage larvae of Anisakis simplex (L3) carried by marine fishes. Human anisakiasis was researched for specific IgG with L3 excretory secretory products (ESP). L3ESP were prepared by daily harvesting of culture supernatant from day 2 to day 5, using two kinds culture media of RPMI-1640 and phosphate buffered saline (PBS). When the sera from persons diagnosed with anisakiasis by means of endoscopy were analyzed using indirect ELISA and Western blot, the sera was classified into four groups depending on specific antigen recognition patterns. In addition, the presence of a new antigen for L3, located at less than 13 kDa (AgLT13) was demonstrated in L3ESP with a modified Western blot condition. The production of AgLT13 was mainly found in L3ESP harvested both on day 2 and day 3, and that in PBS was predominant over that in RPMI-1640. Among those sera, the high reactive sera to L3ESP-day two prepared with phosphate buffer in indirect ELISA recognized AgLT13, and 33% of the low reactive sera did so. These results indicate that the binding pattern of human L3 specific antibody is diverse depending on L3ESP preparations and that AgLT13 demonstrated with a Western blot condition is a specific antigen for L3.