Targeted Therapy for Acute Autoimmune Myocarditis with Nano-Sized Liposomal FK506 in Rats.

Immunosuppressive agents are used for the treatment of immune-mediated myocarditis; however, the need to develop a more effective therapeutic approach remains. Nano-sized liposomes may accumulate in and selectively deliver drugs to an inflammatory lesion with enhanced vascular permeability. The aims of this study were to investigate the distribution of liposomal FK506, an immunosuppressive drug encapsulated within liposomes, and the drug's effects on cardiac function in a rat experimental autoimmune myocarditis (EAM) model.

Treatment of stroke with liposomal neuroprotective agents under cerebral ischemia conditions.

Since the proportion of patients given thrombolytic therapy with tissue plasminogen activator (t-PA) is very limited because of the narrow therapeutic window, the development of new therapies for ischemic stroke has been desired. We previously reported that liposomes injected intravenously accumulate in the ischemic region of the brain via disruption of the blood-brain barrier that occurs under cerebral ischemia. In the present study, we investigated the efficacy of a liposomal neuroprotective agent in middle cerebral artery occlusion (MCAO) rats to develop ischemic stroke therapy prior to the recovery of cerebral blood flow.

Polycation liposomes as a vector for potential intracellular delivery of microRNA.

Background: We previously developed a microRNA (miRNA) delivery system by using dicetyl phosphate-tetraethylenepentamine-based polycation liposomes (TEPA-PCL), applied it to miR-92a delivery, and demonstrated its gene-silencing potential and effective anti-angiogenic effects. In the present study, we investigated the mechanism of intracellular delivery of cholesterol-grafted miR-92a (miR-92a-C) into cells.

Methods: To investigate the intracellular distribution of miR-92a-C/TEPA-PCL complex, we used human umbilical vein endothelial cells and examined certain points after transfection: (i) the time-course of miR-92a-uptake into the cells; (ii) the endocytosis pathway induced by miR-92a-C/TEPA-PCL; (iii) the capability of miR-92a-C/TEPA-PCL to escape from the endosomes; and (iv) the release of miR-92a-C from TEPA-PCL in the cytoplasm.

Development of a miR-92a delivery system for anti-angiogenesis-based cancer therapy.

Background: RNA interference has received much attention as a novel therapeutic strategy. MicroRNA (miRNA) appears to be promising as a novel nucleic-acid medicine because it is able to suppress a series of protein expression that relates to a specific event such as angiogenesis. In the present study, we used dicetyl phosphate-tetraethylenepentamine-based polycation liposomes (TEPA-PCL) as a delivery system for miR-92a, one of the miRNAs regulating angiogenesis, and attempted to deliver miR-92a to angiogenic endothelial cells for the development of cancer therapy by anti-angiogenesis.

Dicetyl phosphate-tetraethylenepentamine-based liposomes for systemic siRNA delivery.

Dicetyl phosphate-tetraethylenepentamine (DCP-TEPA) conjugate was newly synthesized and formed into liposomes for efficient siRNA delivery. Formulation of DCP-TEPA-based polycation liposomes (TEPA-PCL) complexed with siRNA was examined by performing knockdown experiments using stable EGFP-transfected HT1080 human fibrosarcoma cells and siRNA for GFP. An adequate amount of DCP-TEPA in TEPA-PCL and N/P ratio of TEPA-PCL/siRNA complexes were determined based on the knockdown efficiency.

Evaluation of O-[(18)F]fluoromethyl-D-tyrosine as a radiotracer for tumor imaging with positron emission tomography.

O-[(18)F]Fluoromethyl-D-tyrosine (D-[(18)F]FMT) has been reported as a potential tumor-detecting agent for positron emission tomography (PET). However, the reason why D-[(18)F]FMT is better than L-[(18)F]FMT is unclear. To clarify this point, we examined the mechanism of their transport and their suitability for tumor detection.

TRPA1 and TRPV1 activation is a novel adjuvant effect mechanism in contact hypersensitivity.

We have revealed that local stimulation of sensory neurons is involved in the adjuvant effect of dibutyl phthalate (DBP) in a fluorescein isothiocyanate-induced mouse contact hypersensitivity model. Transient receptor potential (TRP) A1 and TRPV1 seemed to be candidate DBP targets. Here we directly demonstrated that DBP activates a subset of neurons in mouse dorsal root ganglia responsive to TRPA1 and TRPV1 agonists.