Extreme stiffness hyperbolic elastic metamaterial for total transmission subwavelength imaging

Subwavelength imaging by metamaterials and extended work to pursue total transmission has been successfully demonstrated with electromagnetic and acoustic waves very recently. However, no elastic counterpart has been reported because earlier attempts suffer from considerable loss. Here, for the first time, we realize an elastic hyperbolic metamaterial lens and experimentally show total transmission subwavelength imaging with measured wave field inside the metamaterial lens. The main idea is to compensate for the decreased impedance in the perforated elastic metamaterial by utilizing extreme stiffness, which has not been independently actualized in a continuum elastic medium so far. The fabricated elastic lens is capable of directly transferring subwavelength information from the input to the output boundary. In the experiment, this intriguing phenomenon is confirmed by scanning the elastic structures inside the lens with laser scanning vibrometer. The proposed elastic metamaterial lens will bring forth significant guidelines for ultrasonic imaging techniquesope

PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1(-/-)) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1(-/-) cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders.</p

Nanomaterials : impact on cells and cell organelles

Colloidal nanoparticles designed for the interactions with cells are very small, nanoscale objects usually consisting of inorganic cores and organic shells that are dispersed in a buffer or biological medium. By tuning the material properties of the nanoparticles a number of different biological applications of nanomaterials are enabled i.e. targeting, labelling, drug delivery, use as diagnostic tools or therapy. For all biological applications of nanoparticles, it is important to understand their interactions with the surrounding biological environment in order to predict their biological impact, in particular when designing the nanoparticles for diagnostic and therapeutic purpose. Due to the high surface-to-volume ratio, the surface of nanomaterials is very reactive. When exposed to biological fluids, the proteins and biomolecules present therein tend to associate with the nanoparticles’ surface. This phenomenon is defined as biomolecular corona formation. The biomolecular corona plays a key role in the interaction between nanoparticles and biological systems, impacting on how these particles interact with biological systems on a cellular and molecular level. This book chapter describes the nature of the interactions at the bio-nano interface, shows the design strategy of nanoparticles for nanomedicine, and defines the concepts of biomolecular corona and biological identity of nanoparticles. Moreover, it describes the interaction of functionalised nanomaterials with cell organelles and intracellular fate of nanoparticles and it shows therapeutic application of gold nanoparticles as dose enhancers in radiotherapy