Apoptotic Cell Membrane-Inspired Polymer for Immunosuppression

Apoptotic cell death serves important roles in homeostasis by eliminating dangerous, damaged, or unnecessary cells without causing an inflammatory response by externalizing phosphatidylserine to the outer leaflet in the phospholipid bilayer. In this study, we newly designed apoptotic cell membrane-inspired monomer and polymer which have the phosphoryl serine group as the anti-inflammatory functional moiety and demonstrate here for the first time that administration of an apoptotic cell membrane-inspired phosphorylserine polymer can protect murine macrophages (RAW 264.7) from lipopolysaccharide-induced inflammation. Interestingly, statistical copolymers with phosphorylcholine monomer that mimicked more precisely the apoptotic cell membrane result in more effective suppression of macrophage activation. This study provides new insights into the rational design of effective polymeric materials for anti-inflammatory therapies

Nano-Decoration of the Hemagglutinating Virus of Japan Envelope (HVJ-E) Using a Layer-by-Layer Assembly Technique

In this study, we created a nanoscale layer of hyaluronic acid (HA) on the inactivated Hemagglutinating Virus of Japan envelope (HVJ-E) via a layer-by-layer (LbL) assembly technique for CD-44 targeted delivery. HVJ-E was selected as the template virus because it has shown a tumor-suppressing ability by eliciting inflammatory cytokine production in dendritic cells. Although it has been required to increase the tumor-targeting ability and reduce nonspecific binding because HVJ-E fuses with virtually all cells and induces hemagglutination in the bloodstream, complete modifications of single-envelope-type viruses with HA have been difficult. Therefore, we studied the surface ζ potential of HVJ-E at different pH values and carefully examined the deposition conditions for the first layer using three cationic polymers: poly-l-lysine (PLL), chitosan (CH), and glycol chitosan (GC). GC-coated HVJ-E particles showed the highest disperse ability under physiological pH and salt conditions without aggregation. An HA layer was then prepared via alternating deposition of HA and GC. The successive decoration of multilayers on HVJ-E has been confirmed by dynamic light scattering (DLS), ζ potentials, and transmission electron microscopy (TEM). An enzymatic degradation assay revealed that only the outermost HA layer was selectively degraded by hyaluronidase. However, entire layers were destabilized at lower pH. Therefore, the HA/GC-coated HVJ-E describe here can be thought of as a potential bomb for cancer immunotherapy because of the ability of targeting CD44 as well as the explosion of nanodecorated HA/GC layers at endosomal pH while preventing nonspecific binding at physiological pH and salt conditions such as in the bloodstream or normal tissues

Simple Coating with pH-Responsive Polymer-Functionalized Silica Nanoparticles of Mixed Sizes for Controlled Surface Properties

Different-sized silica nanoparticles (SiNPs) were functionalized by pH-responsive poly­(2-(diisopropylamino)­ethyl methacrylate) (PDP) via surface-initiated atom transfer radical polymerization (ATRP). The functionalized PDP-SiNPs were used to coat glass surfaces, polymeric nanofibers, and paper via simple coating methods such as dip, cast, and spray coating. A PDP-SiNPs mixture having different sizes was found to change the surface properties of the substrates remarkably, compared to one containing PDP-SiNPs with uniform sizes. High surface roughness was achieved with very little coating materials, which is beneficial from an economical point of view. Moreover, adsorption/desorption of PDP-SiNPs onto/from the substrates could be controlled by changing solution pH due to the protonation/deprotonation of the PDP. The surface properties of the coated substrates were analyzed by contact angle (CA) measurement, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). This inexpensive system provides a simple, quick, and effective approach to changing the surface properties of substrates that could be exploited for large-scale surface modification

Hippo Pathway Effectors Control Cardiac Progenitor Cell Fate by Acting as Dynamic Sensors of Substrate Mechanics and Nanostructure

Stem cell responsiveness to extracellular matrix (ECM) composition and mechanical cues has been the subject of a number of investigations so far, yet the molecular mechanisms underlying stem cell mechano-biology still need full clarification. Here we demonstrate that the paralog proteins YAP and TAZ exert a crucial role in adult cardiac progenitor cell mechano-sensing and fate decision. Cardiac progenitors respond to dynamic modifications in substrate rigidity and nanopattern by promptly changing YAP/TAZ intracellular localization. We identify a novel activity of YAP and TAZ in the regulation of tubulogenesis in 3D environments and highlight a role for YAP/TAZ in cardiac progenitor proliferation and differentiation. Furthermore, we show that YAP/TAZ expression is triggered in the heart cells located at the infarct border zone. Our results suggest a fundamental role for the YAP/TAZ axis in the response of resident progenitor cells to the modifications in micro­environment nanostructure and mechanics, thereby contributing to the maintenance of myocardial homeostasis in the adult heart. These proteins are indicated as potential targets to control cardiac progenitor cell fate by materials design