An albumin scaffold grafted with an alpha-helical motif delivers therapeutic payloads by modular coiled-coil assembly.

A short in vivo half-life of protein-based therapeutics often restricts successful clinical translation despite their promising efficacy in vitro. As a biocompatible half-life extender, human serum albumin (HSA) has proven effective in some cases. While genetic fusion is well-established for interlinking HSA and a protein payload, it is limited to structurally simple proteins, necessitating new strategies to expand the utility of HSA for delivery of therapeutic proteins. Here, we report a novel HSA variant (eHSA) as a modular and long-acting carrier compatible with any protein payload of interest. The assembly between eHSA and a payload was driven by a heterodimeric coiled-coil interaction in which a short α-helix grafted onto HSA specifically bound to a complementary α-helix genetically fused to a payload. We showed various proteins including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), single-chain TRAIL, or green fluorescent protein could piggyback onto eHSA via simple mixing without losing native activity. Additionally, either in presence or absence of a payload, eHSA was found to retain the pH-dependent FcRn-binding behavior - a critical attribute for prolonged survival in the systemic circulation. These results demonstrate eHSA would serve as a modular platform capable of delivering various therapeutic proteins with potentially long in vivo half-lives.

Nanotechnology as a promising platform for rheumatoid arthritis management: Diagnosis, treatment, and treatment monitoring.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that develops in about 5 per 1000 people. Over the past years, substantial progresses in knowledge of the disease's pathophysiology, effective diagnosis methods, early detection, and efficient treatment strategies have been made. Notably, nanotechnology has emerged as a game-changer in the efficacious management of many diseases, especially for RA. Joint replacement, photothermal therapy (PTT), photodynamic therapy (PDT), RA diagnosis, and treatment monitoring are nano-based avenues in RA management. Here, we present a brief overview of the pathogenesis of RA, risk factors, conventional diagnostic methods and treatment approaches, and then discuss the role of nanomedicine in RA diagnosis, treatment, and treatment monitoring with an emphasis on functional characteristics distinctive from other RA therapeutics.

Optimized immobilization of endoglucanase Cel9A onto glutaraldehyde activated chitosan nanoparticles by response surface methodology: The study of kinetic behaviors.

Immobilization of enzyme onto nanoparticles such as chitosan can have biotechnological importance. In this study, chitosan nanoparticles (ChNPs) were prepared by Ionic gelation method and Endoglucanase Cel9A from Alicyclobacillus acidocaldariius (AaCel9A) immobilized on the nanoparticles. The FTIR results showed that the enzymes were immobilized on the ChNPs. The dynamic light scattering and scanning electron microscope (SEM) results illustrated that the AaCel9A-ChNPs approximately had 40 nm diameters. For optimizing enzyme immobilization, response surface methodology was employed using different variables (pH, enzyme immobilization time, and enzyme to ChNPs ratio [E/Cs]). The results showed that the high immobilization efficiency was achieved in pH 7, E/Cs of 0.4 in 2.63 hr. The enzyme activity results showed that, immobilization increased optimum pH for activity (from 6.5 to 7.5) and the enzyme Km (from 3.703 to 12.195 [mg/ml]), which make it suitable to use in some industries such as detergents.

Deleting the Ig-Like Domain of Alicyclobacillus acidocaldarius Endoglucanase Cel9A Causes a Simultaneous Increase in the Activity and Stability.

Endoglucanase Cel9A from Alicyclobacillus acidocaldarius (AaCel9A) is a monomeric enzyme with 537 residues. This enzyme has an Ig-like domain in the N-terminus of the catalytic domain. In this study, the role of the Ig-like domain on the activity, stability, and structural rigidity of AaCel9A and the effect of calcium on enzyme activity and stability were examined by comparing a truncated enzyme with deletion of the Ig-like domain (AaCel9AΔN) to the wild-type enzyme. Our results showed that the deletion of the Ig-like domain increased the catalytic efficiency of the truncated enzyme up to threefold without any significant changes in the K m of the enzyme. Furthermore, pH and temperature optimum for activity were shifted from 6.5 to 7.5 and from 65 to 60 °C, respectively, by deletion of the Ig-like domain. The thermal stability and fluorescence quenching results indicated that the stability and rigidity of the truncated enzyme have been more than that of the wild-type enzyme. Calcium similarly increased the catalytic efficiency of the enzymes (up to 40 %) and remarkably raised the stability of the AaCel9A compared to the AaCel9AΔN. This shows that Ig-like domain has a role in the increase of the enzyme stability by calcium in the wild-type enzyme.