Functionalization of polymeric nanoparticles with targeting VNAR ligands using vinyl sulfone conjugation.

Actively targeted drug loaded nanoparticles represent an exciting new form of therapeutics for cancer and other diseases. These formulations are complex and in order to realize their ultimate potential, optimization of their preparation is required. In this current study, we have examined the conjugation of a model targeting ligand, conjugated in a site-specific manner using a vinyl sulfone coupling approach. A disulfide-functionalized poly(L-lactide)-b-poly(oligo(ethylene glycol) methacrylate)-stat-(bis(2-methacryloyl)oxyethyl disulfide) (PLA-b-P(OEGMA-stat-DSDMA)) diblock copolymer was synthesized by simultaneous ring opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. Subsequently, the disulfide bonds of the polymer were reduced to thiols and divinyl sulfone was attached to the polymer using thiol-ene chemistry to produce the vinyl sulfone (VS)-functionalized PLA-b-P(OEGMA-stat-VSTEMA) amphiphilic block copolymer. Single emulsion - solvent evaporation was employed using a blend of this polymer with poly(D,L-lactide-co-glycolide) (PLGA) to produce VS-functionalized polymeric nanoparticles. The ability of these novel nanoparticles to attach ligands was then exemplified using a single domain variable new antigen receptor (VNAR) with a free carboxyl terminal cysteine residue. The resulting VNAR-functionalized nanoparticles were found to maintain specific affinity to their cognate antigen (DLL4) for at least 72 h at 4 °C. The simplicity of the degradable amphiphilic block copolymer synthesis and the efficiency of VNAR conjugation to the VS-functionalized nanoparticles show the potential of this platform for therapeutic development.

ECB unconventional monetary policy and SME access to finance.

Small- and medium-sized enterprises (SMEs) account for two-thirds of employment in the euro area which makes them a priority for the transmission of monetary policy to the real economy. SMEs in Europe experienced a credit crunch following the sovereign debt crisis. Over the period 2014-2019, the European Central Bank (ECB) engaged in unconventional monetary policy (UMP) to restore funding conditions in the euro area, to support stronger economic growth and higher inflation. We use the ECB/EC Survey on the Access to Finance of Enterprises to examine the relationship between monetary policy and SME access to finance in countries that were most affected by the crisis as follows: Greece, Ireland, Italy, Portugal and Spain. We show that the implementation of UMP increases the probability that firms with higher debt-to-assets ratio remain credit constrained in stressed countries, although this effect becomes insignificant in non-stressed countries. Our findings suggest that monetary policy is transmitted unevenly to leveraged SMEs across jurisdictions. Additionally, we find little evidence that risky firms are credit constrained during periods of UMP, when risk is measured from the firms' own viewpoint. However, our heterogenous analysis shows that smaller and younger firms-which are also considered to be risky-remain credit constrained over this period. Policy should ensure that UMP trickles down to SMEs regardless of their size, age or location. Tweetable line: Leveraged SMEs in stressed countries are more likely to remain credit constrained even when monetary policy is expansionary. Policy must do more to support small and young firms' access to credit to facilitate higher investment and growth.

Wholly Biobased, Highly Stretchable, Hydrophobic, and Self-healing Thermoplastic Elastomer.

Renewable polymers with excellent stretchability and self-healing ability are interesting for a wide range of applications. A novel type of wholly biobased, self-healing, polyamide-based thermoplastic elastomer was synthesized using a fatty dimer acid and a fatty dimer amine, both containing multiple alkyl chains, through facile one-pot condensation polymerization under different polymerization times. The resulting elastomer shows superior stretchability (up to 2286%), high toughness, and excellent shape recovery after being stretched to different strains. This elastomer also displays high room-temperature autonomous self-healing efficiency after fracture and zero water uptake during water immersion. The highly entangled main chain, the multiple dangling chains, the abundant reversible physical bonds, the intermolecular diffusion, and the low ratio of amide to methylene group within the elastomer are responsible for these extraordinary properties. The polymerization time influences the properties of the elastomer. The use of the optimal self-healing thermoplastic elastomer in anticorrosion coating, piezoresistive sensing, and highly stretchable fibers is also demonstrated. The elastomer coating prevents stainless-steel products from corrosion in a salty environment due to its superhydrophobicity. The elastomer serves as a robust flexible substrate for creating self-healing piezoresistive sensors with excellent repeatability and self-healing efficiency. The elastomer fiber yarn can be stretched to 950% of its original length confirming its outstanding stretchability.