Delivery technologies for therapeutic targeting of fibronectin in autoimmunity and fibrosis applications.

Fibronectin (FN) is a critical component of the extracellular matrix (ECM) contributing to various physiological processes, including tissue repair and immune response regulation. FN regulates various cellular functions such as adhesion, proliferation, migration, differentiation, and cytokine release. Alterations in FN expression, deposition, and molecular structure can profoundly impact its interaction with other ECM proteins, growth factors, cells, and associated signaling pathways, thus influencing the progress of diseases such as fibrosis and autoimmune disorders. Therefore, developing therapeutics that directly target FN or its interaction with cells and other ECM components can be an intriguing approach to address autoimmune and fibrosis pathogenesis.

Nanoparticle protein corona: from structure and function to therapeutic targeting.

Nanoparticle (NP)-based therapeutics have ushered in a new era in translational medicine. However, despite the clinical success of NP technology, it is not well-understood how NPs fundamentally change in biological environments. When introduced into physiological fluids, NPs are coated by proteins, forming a protein corona (PC). The PC has the potential to endow NPs with a new identity and alter their bioactivity, stability, and destination. Additionally, the conformation of proteins is sensitive to their physical and chemical surroundings. Therefore, biological factors and protein-NP-interactions can induce changes in the conformation and orientation of proteins in vivo. Since the function of a protein is closely connected to its folded structure, slight differences in the surrounding environment as well as the surface characteristics of the NP materials may cause proteins to lose or gain a function. As a result, this can alter the downstream functionality of the NPs. This review introduces the main biological factors affecting the conformation of proteins associated with the PC. Then, four types of NPs with extensive utility in biomedical applications are described in greater detail, focusing on the conformation and orientation of adsorbed proteins. This is followed by a discussion on the instances in which the conformation of adsorbed proteins can be leveraged for therapeutic purposes, such as controlling protein conformation in assembled matrices in tissue, as well as controlling the PC conformation for modulating immune responses. The review concludes with a perspective on the remaining challenges and unexplored areas at the interface of PC and NP research.

Synthesis and characterization of Schiff base containing bovine serum albumin-gum arabic aldehyde hybrid nanogels via inverse miniemulsion for delivery of anticancer drug.

The periodate modified gum arabic was used as a natural-based, non-toxic cross-linker to synthesize hybrid bovine serum albumin-gum arabic aldehyde (BSA-GAA) nanogels by Schiff base reaction through the inverse miniemulsion method for the first time. The synthesis process was performed in the absence of toxic organic solvents using fractionated coconut oil as the continuous phase. The particle size of the nanogels was managed by tweaking the concentration of the surfactants (Span 80/Tween 80) and the total volume of the aqueous phase. Based on the bicinchoninic acid method, the cross-linking efficiency of BSA and GAA was estimated at 98%. 5-fluorouracil (5-FU) was selected as the sample drug. The 5-FU-loaded hybrid nanogels showed a spherical morphology with an average diameter of 231.33 ±12.74 nm and a zeta potential of -31.6 mV. The encapsulation and loading efficiency of the nanogels were calculated at 42 ± 4.52% and 2.37 ± 0.59%, respectively. The properties of the hybrid nanogels were analyzed by dynamic light scattering (DLS), Fourier transform infrared microscopy (FTIR) analysis, field emission scanning electron microscopy (FE-SEM), and thermogravimetric analysis (TGA). The pH sensitivity of the hybrid nanogels was confirmed by the in vitro release profiles of 5-FU in different buffers. Hemolysis assay revealed the in vitro hemocompatibility of the hybrid nanogels which inhibited the growth of MCF-7 cells with an IC50 value of 16.21 µM. The present study suggested that these biobased hybrid nanogels could have a great potential in drug delivery and other biomedical applications.

Assessing virus like particles formation and r-HBsAg aggregation during large scale production of recombinant hepatitis B surface antigen from Pichia pastoris.

The aggregation of recombinant proteins in the different stages of purification leads to the loss of a considerable portion of target protein and reduction in the process efficiency. As the active HBsAg used in Hepatitis B vaccine production is in the form of virus-like particle (VLP), therefore the time and stages at which the VLP assembling happened through the process would be important. The aim of this study was to explore the product aggregation during different stages of large scale production of rHBsAg in Pichia pastoris at production unit of the Pasteur Institute of Iran. Dynamic light scattering (DLS) and transmission electron microscopy (TEM), and also size exclusion-high-performance liquid chromatography (SE-HPLC) were carried out on samples taken from each downstream processes steps to determine the rate of VLPs formation as the desired product and the aggregated form at each stage of the purification. Based on the results, it was found that VLPs formation started at the acid precipitation stage and reached up to 80% at the thermal treatment stage. The ultrafiltration, ion exchange chromatography and immunoaffinity chromatography stages were disclosed to have the highest contribution in the formation of VLP (virus like particle) 22 nm.