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Amino acids show promise as versatile biomolecules for creating a variety of functional biomaterials. Previously, we discovered a novel amino acid reaction, in which a single amino acid can form browning species in a simple solvent mixture comprising DMSO and acetone at room temperature. In the present study, we initially conducted a comprehensive analysis of 190 pairs of binary amino acids (i.e., all the possible pairwise combinations out of 20 amino acids) and identified several surprising combinations that exhibited synergistic browning effects. Particularly, cysteine–lysine and cysteine–arginine pairs exhibited pronounced browning in DMSO/acetone cosolvent solutions. We hypothesize that the coloured species result from the formation of extended, hydrophobic molecules with highly conjugated systems, arising from extensive condensation reactions between amino acids. Subsequently, we aimed at developing a nano-platform based on this newly discovered amino acid reaction. We demonstrate that through a nanoprecipitation process (solvent-shifting), spherical nanoparticles with sizes ranging from 100 to 200 nm can be produced, in the presence of ferric ions added to the water phase. Through systematic optimization and comprehensive characterization, the final product is a zwitterionic, charge-reversible nanoparticle featuring three functional groups on its surface: carboxylates, amines, and thiols. Furthermore, it possesses mild antioxidant activity, making it a new type of nano-antioxidant. Finally, we present preliminary results highlighting the potential of using this new nanomaterial as a delivery system for polynucleotides. In conclusion, the paper introduces a novel class of amino acid-derived nanoparticles with significant promise for future biomedical applications. [ABSTRACT FROM AUTHOR]

Amphiphilic drugs are therapeutic agents whose molecular structures contain both hydrophobic and hydrophilic portions. Here we report a systematic study on how amphiphilic drugs can assist in silica nanoprecipitation. 3-Mercaptopropyltrimethoxysilane (MPTMS) was used as the sole silica material and 12 amphiphilic drugs spanning a wide spectrum of therapeutic categories were included. MPTMS polycondensation was conducted in a DMSO-based organic phase. After a sufficient time, particle formation was induced by injecting a small amount of the organic phase into a water solution containing various amphiphiles. The results show that all amphiphilic drugs studied exerted concentration-dependent facilitating effect on nanoparticle formation. Under certain preparation conditions, the particle solution showed physical stability over a long period and the formed particles could be as small as 100 nm. By systematically varying drug concentrations and injection volumes, the ability of each amphiphile to promote nanoprecipitation can be quantified and compared, based on two novel indices: the area under the critical volume-concentration curve (AUC) and the critical stabilization concentration (CSC). We demonstrate that both ability indices significantly correlated with the drug's log P and critical micelle concentrations (CMC). Furthermore, we have optimized the aging and particle purification condition and extensively characterized our system through comprehensive TEM and zeta-potential measurements, as well as determinations for drug entrapment and release. In conclusion, we have established a quantitative structure-activity relationship for amphiphilic small-molecular drugs in their ability to interact with poly(mercaptopropyl)silsesquioxane species and form nanoparticles via solvent shifting. We speculate that both hydrophobic and electrostatic interactions play important roles in the formation and stabilization of nanoparticles.

In this article, we report a novel, nanoprecipitation-based method for preparing silica nanoparticles with thiol and amine cofunctionalization. (3-Mercaptopropyl)trimethoxysilane (MPTMS) and 3-aminopropyltrimethoxysilane (APTMS) were used as the organosilane precursors, which were subjected to acid-catalyzed polycondensation in an organic phase containing a water-miscible solvent (e.g., dimethyl sulfoxide). A pale colloidal solution could be immediately formed when the preincubated organic phase was directly injected into water. The initial composition ratio between MPTMS and APTMS is an important factor governing the formation of nanoparticles. Specifically, large, unstable micrometer-sized particles were formed for preparation using MPTMS as the sole silane source. In contrast, when APTMS was used alone, no particles could be formed. By reducing the fraction of APTMS (or increasing that of MPTMS) in the initial mixture of organosilanes, the formation of nanometer-sized particles occurred at a critical fraction of APTMS (i.e., 25%). Remarkably, a tiny fraction (e.g., 1%) of APTMS was sufficient to produce stable nanoparticles with a hydrodynamic diameter of about 200 nm. Other factors that would also affect particle formation were determined. Moreover, an interesting temperature effect on particle formation was observed. The TEM micrographs show spherical nanospheres with mean sizes of 130-150 nm in diameter. The solid-state (29)Si NMR spectra demonstrate that the hybrid silica materials contain fully and partially condensed silicon structures. The bifunctionalized silica nanoparticles have positive zeta potentials whose magnitudes are positively correlated with the amount of APTMS. The total thiol content, however, is negatively correlated with the amount of APTMS. The cationic nanoparticles can bind an antisense oligonucleotide in a composition-dependent manner.