Light-induced release of the cardioprotective peptide angiotensin-(1-9) from thermosensitive liposomes with gold nanoclusters.

Angiotensin-(1-9), a component of the non-canonical renin-angiotensin system, has a short half-life in blood. This peptide has shown to prevent and/or attenuate hypertension and cardiovascular remodeling. A controlled release of angiotensin-(1-9) is needed for its delivery to the heart. Our aim was to develop a drug delivery system for angiotensin-(1-9). Thermosensitive liposomes (LipoTherm) were prepared with gold nanoclusters (LipoTherm-AuNC) to increase the stability and reach a temporal and spatial control of angiotensin-(1-9) release. Encapsulation efficiencies of nearly 50% were achieved in LipoTherm, reaching a total angiotensin-(1-9) loading of around 180 µM. This angiotensin-(1-9)-loaded LipoTherm sized around 100 nm and exhibited a phase transition temperature of 43 °C. AuNC were grown on LipoTherm and the new hybrid nanosystem showed energy absorption in the near-infrared (NIR) wavelength range. By NIR laser irradiation, a controlled release of angiotensin-(1-9) was achieved from the LipoTherm-AuNC nanosystem. These nanosystems did not show any cytotoxic effect on cultured cardiomyocytes. Biological activity of angiotensin-(1-9) released from the LipoTherm-AuNC-based nanosystem was confirmed using an ex vivo Langendorff heart model.

Nanoparticles for diagnosis and therapy of atherosclerosis and myocardial infarction: evolution toward prospective theranostic approaches.

Cardiovascular diseases are the leading cause of death worldwide. Despite preventive efforts, early detection of atherosclerosis, the common pathophysiological mechanism underlying cardiovascular diseases remains elusive, and overt coronary artery disease or myocardial infarction is often the first clinical manifestation. Nanoparticles represent a novel strategy for prevention, diagnosis, and treatment of atherosclerosis, and new multifunctional nanoparticles with combined diagnostic and therapeutic capacities hold the promise for theranostic approaches to this disease. This review focuses on the development of nanosystems for therapy and diagnosis of subclinical atherosclerosis, coronary artery disease, and myocardial infarction and the evolution of nanosystems as theranostic tools. We also discuss the use of nanoparticles in noninvasive imaging, targeted drug delivery, photothermal therapies together with the challenges faced by nanosystems during clinical translation.

The enzymes LSD1 and Set1A cooperate with the viral protein HBx to establish an active hepatitis B viral chromatin state.

With about 350 million people chronically infected around the world hepatitis B is a major health problem. Template for progeny HBV synthesis is the viral genome, organized as a minichromosome (cccDNA) inside the hepatocyte nucleus. How viral cccDNA gene expression is regulated by its chromatin structure; more importantly, how the modulation of this structure impacts on viral gene expression remains elusive. Here, we found that the enzyme SetDB1 contributes to setting up a repressed cccDNA chromatin state. This repressive state is activated by the histone lysine demethylase-1 (LSD1). Consistently, inhibiting or reducing LSD1 levels led to repression of viral gene expression. This correlates with the transcriptionally repressive mark H3K9 methylation and reduction on the activating marks H3 acetylation and H3K4 methylation on viral promoters. Investigating the importance of viral proteins we found that LSD1 recruitment to viral promoters was dependent on the viral transactivator protein HBx. Moreover, the histone methyltransferase Set1A and HBx are simultaneously bound to the core promoter, and Set1A expression correlates with cccDNA H3K4 methylation. Our results shed light on the mechanisms of HBV regulation mediated by the cccDNA chromatin structure, offering new therapeutic targets to develop drugs for the treatment of chronically infected HBV patients.