Formulation matters! A spectroscopic and molecular dynamics investigation on the peptide CIGB552 as itself and in its therapeutical formulation.

Synthetic therapeutic peptides (STP) are intensively studied as new-generation drugs, characterized by high purity, biocompatibility, selectivity and stereochemical control. However, most of the studies are focussed on the bioactivity of STP without considering how the formulation actually used for therapy administration could alter the physico-chemical properties of the active principle. The aggregation properties of a 20-mer STP (Ac-His-Ala-Arg-Ile-Lys-D-Pro-Thr-Phe-Arg-Arg-D-Leu-Lys-Trp-Lys-Tyr-Lys-Gly-Lys-Phe-Trp-NH2 ), showing antitumor activity, were investigated by optical spectroscopy and atomic force microscopy imaging, as itself (CIGB552) and in its therapeutic formulation (CIGB552TF). It has found that the therapeutic formulation deeply affects the aggregation properties of the investigated peptide and the morphology of the aggregates formed on mica by deposition of CIGB552 and CIGB552TF millimolar solutions. Molecular dynamics simulations studied the first steps of CIGB552 aggregation under physiological ionic strength conditions (NaCl 150 mM), showing that peptide oligomers, from dimers to tetramers, are preferentially formed in this environment. Interestingly, cell viability assays performed on H-460 cell lines indicate a major antiproliferative activity of the peptide in its therapeutic formulation with respect to the peptide aqueous solution.

Programmable Phototaxis of Metal-Phenolic Particle Microswimmers.

Light-driven directional motion is common in nature but remains a challenge for synthetic microparticles, particularly regarding collective motion on a macroscopic scale. Successfully engineering microparticles with light-driven collective motion could lead to breakthroughs in drug delivery, contaminant sensing, environmental remediation, and artificial life. Herein, metal-phenolic particle microswimmers capable of autonomously sensing and swimming toward an external light source are reported, with the speed regulated by the wavelength and intensity of illumination. These microswimmers can travel macroscopic distances (centimeters) and can remain illuminated for hours without degradation of motility. Experimental and theoretical analyses demonstrate that motion is generated through chemical transformations of the organic component of the metal-phenolic complex. Furthermore, cargos with specific spectral absorption profiles can be loaded into the particles and endow the particle microswimmers with activated motion corresponding to these spectral characteristics. The programmable nature of the light navigation, tunable size of the particles, and versatility of cargo loading demonstrate the versatility of these metal-phenolic particle microswimmers.

Porphyrins Through the Looking Glass: Spectroscopic and Mechanistic Insights in Supramolecular Chirogenesis of New Self-Assembled Porphyrin Derivatives.

The solvent driven aggregation of porphyrin derivatives, covalently linked to a L- or D-prolinate enantiomer, results in the stereospecific formation of species featuring remarkable supramolecular chirality, as a consequence of reading and amplification of the stereochemical information stored in the proline-appended group. Spectroscopic, kinetic, and topographic SEM studies gave important information on the aggregation processes, and on the structures of the final chiral architectures. The results obtained may be the seeds for the construction of stereoselective sensors aiming at the detection, for example, of novel emergent pollutants from agrochemical, food, and pharmaceutical industry.

Tunable Supramolecular Chirogenesis in the Self-Assembling of Amphiphilic Porphyrin Triggered by Chiral Amines.

Supramolecular chirality is one of the most important issues in different branches of science and technology, as stereoselective molecular recognition, catalysis, and sensors. In this paper, we report on the self-assembly of amphiphilic porphyrin derivatives possessing a chiral information on the periphery of the macrocycle (i.e., D- or L-proline moieties), in the presence of chiral amines as co-solute, such as chiral benzylamine derivatives. The aggregation process, steered by hydrophobic effect, has been studied in aqueous solvent mixtures by combined spectroscopic and topographic techniques. The results obtained pointed out a dramatic effect of these ligands on the morphology and on the supramolecular chirality of the final self-assembled structures. Scanning electron microscopy topography, as well as fluorescence microscopy studies revealed the formation of rod-like structures of micrometric size, different from the fractal structures formerly observed when the self-assembly process is carried out in the absence of chiral amine co-solutes. On the other hand, comparative experiments with an achiral porphyrin analogue strongly suggested that the presence of the prolinate moiety is mandatory for the achievement of the observed highly organized suprastructures. The results obtained would be of importance for unraveling the intimate mechanisms operating in the selection of the homochirality, and for the preparation of sensitive materials for the detection of chiral analytes, with tunable stereoselectivity and morphology.

Protein Component of Oyster Glycogen Nanoparticles: An Anchor Point for Functionalization.

Biosourced nanoparticles have a range of desirable properties for therapeutic applications, including biodegradability and low immunogenicity. Glycogen, a natural polysaccharide nanoparticle, has garnered much interest as a component of advanced therapeutic materials. However, functionalizing glycogen for use as a therapeutic material typically involves synthetic approaches that can negatively affect the intrinsic physiological properties of glycogen. Herein, the protein component of glycogen is examined as an anchor point for the photopolymerization of functional poly(N-isopropylacrylamide) (PNIPAM) polymers. Oyster glycogen (OG) nanoparticles partially degrade to smaller spherical particles in the presence of protease enzymes, reflecting a population of surface-bound proteins on the polysaccharide. The grafting of PNIPAM to the native protein component of OG produces OG-PNIPAM nanoparticles of ∼45 nm in diameter and 6.2 MDa in molecular weight. PNIPAM endows the nanoparticles with temperature-responsive aggregation properties that are controllable and reversible and that can be removed by the biodegradation of the protein. The OG-PNIPAM nanoparticles retain the native biodegradability of glycogen. Whole blood incubation assays revealed that the OG-PNIPAM nanoparticles have a low cell association and inflammatory response similar to that of OG. The reported strategy provides functionalized glycogen nanomaterials that retain their inherent biodegradability and low immune cell association.