Pancreatic cancer is one of the most common forms of malignant disease with a poor survival prognosis. Currently, nanomedicine holds great promise for targeted diagnosis and treatment of this cancer, which also reduces toxic side effects. In this work, we prepared PEG-coated monodisperse upconversion nanoparticles (UCNPs) with a conjugated Flamma® fluorescent dye for imaging and detection of particle distribution in vivo. We performed a thorough physicochemical characterization of the particles and determined their colloidal and chemical stability in several aqueous media such as water, PBS, Dulbecco's modified Eagle's medium and artificial lysosomal fluid. Luminescence resonance energy transfer from the emission of UCNPs as a donor to the Flamma® as an acceptor was confirmed. Intraperitoneal versus intravenous administration was then compared in terms of biodistribution of particles in various organs in the orthotopic mice pancreatic cancer model. The intraperitoneal route was preferred over the intravenous one, because it significantly increased the accumulation of particles in the tumor tissue. These new UCNP@Ale-PEG-Flamma® nanoparticles are thus promising for new treatment avenues for pancreatic cancer.

• Publication type
• Journal Article MeSH

Iron is an essential mineral participating in numerous biological processes in the organism under physiological conditions. However, it may be also involved in the pathological mechanisms activated in various cardiovascular diseases including myocardial ischemia/reperfusion (I/R) injury, due to its involvement in reactive oxygen species (ROS) production. Furthermore, iron has been reported to participate in the mechanisms of iron-dependent cell death defined as "ferroptosis". On the other hand, iron may be also involved in the adaptive processes of ischemic preconditioning (IPC). This study aimed to elucidate whether small amounts of iron may modify the cardiac response to I/R in isolated perfused rat hearts and their protection by IPC. Pretreatment of the hearts with iron nanoparticles 15 min prior to sustained ischemia (iron preconditioning, Fe-PC) did not attenuate post-I/R contractile dysfunction. Recovery of left ventricular developed pressure (LVDP) was significantly improved only in the group with combined pretreatment with iron and IPC. Similarly, the rates of contraction and relaxation [+/-(dP/dt)max] were almost completely restored in the group preconditioned with a combination of iron and IPC but not with iron alone. In addition, the severity of reperfusion arrhythmias was reduced only in the iron+IPC group. No changes in protein levels of "survival" kinases of the RISK pathway (Reperfusion Injury Salvage Kinase) were found except for reduced caspase 3 levels in both preconditioned groups. The results indicate that a failure to precondition rat hearts with iron may be associated with the absent upregulation of RISK proteins and the pro-ferroptotic effect manifested by reduced glutathione peroxidase 4 (GPX4) levels. However, combination with IPC suppressed the negative effects of iron resulting in cardioprotection.

• MeSH
• Ischemic Preconditioning, Myocardial * MeSH
• Rats MeSH
• Myocardium metabolism   MeSH
• Rats, Wistar MeSH
• Ischemic Preconditioning * methods   MeSH
• Myocardial Reperfusion Injury * metabolism   MeSH
• Heart MeSH
• Iron metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Iron MeSH