Teh-Min Hu

Solvent-mediated browning has recently emerged as a distinctive mode of chemical transformation in solution-phase chemistry. In this study, we extend this concept to biogenic indoles and show that an organocatalytic browning process can be achieved in a mixed DMSO/acetone system under mild, catalyst-free conditions. Tryptamine, a decarboxylated metabolite of L-tryptophan, underwent spontaneous browning despite lacking the zwitterionic framework characteristic of amino acids. Notably, the presence of indole-3-acetic acid (I3AA) markedly intensified the reaction and accelerated mesityl oxide formation, indicating a cooperative catalytic effect on acetone self-condensation. Upon transfer of the browned reaction mixtures into water, the hydrophobic products became supersaturated and spontaneously assembled into uniform nanoparticles via liquid–liquid nanoprecipitation. The resulting browned indole-derived nanoparticles exhibited spherical morphology, pH-responsive surface charge reversal near pH 9, and stable electrostatic association with the model polynucleotide G3139. Overall, this work illustrates how intermolecular interactions and reaction chemistry in organic solvents can be coupled with solvent exchange to drive the bottom-up formation of zwitterionic soft-matter nanostructures, providing a simple and versatile route to biogenic colloidal systems.

Gastroretentive drug delivery systems (GRDDS) are attractive oral extended-release dosage forms that prolong drug release and absorption in the gastrointestinal tract through engineered mechanisms to extend the residence time of orally administered dosage forms in the stomach. One of the gastroretentive designs is to render the dosage forms floatable in the gastric fluid upon oral administration. The present study aimed to develop albumin cryogels with extended buoyancy and remarkable resistance to gastric proteolysis. Protein hydrogel monoliths can be prepared through thiol-organosilane-mediated hydrogelation of bovine serum albumin, followed by lyophilization to remove water, thereby producing cryogels. The study demonstrates that, by adjusting the composition of Na₂HPO₄ and sodium alginate in the hydrogel formulation, protein degradability can be effectively tuned to produce an intact floating structure with sustained buoyancy for over 24 h in simulated gastric fluid. This result is consistent with the finding that fluorescein, as a model payload, generally exhibited a decreased release rate from the formulations with increasing concentrations of Na₂HPO₄ and alginate. Notably, above a threshold concentration (i.e., about 2%) of alginate, the hydrogel monolith rapidly disintegrated in nearly neutral environments such as water and simulated intestinal fluid, exhibiting pH-responsive characteristics. Finally, the generalizability of the albumin-organosilane-alginate system as a promising controlled-release platform is further demonstrated in expanded application examples, using doxorubicin, mitoxantrone, methylene blue, and rhodamine 6G as the loaded payload; all exhibiting reproducible controlled-release profiles for the alginate-doped formulation. This finding can be explained by the SEM images showing smaller and denser porous structures with thicker, fiber-tangled intercompartment walls for gels with high alginate concentrations. Overall, the freeze-dried albumin-organosilane-alginate cryogel formulation demonstrates excellent buoyancy, resistance to degradation by simulated gastric fluid, and the ability to regulate drug release, highlighting its feasibility as a GRDDS.

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.

This study explores the surprising browning reaction of tryptophan in acetone/DMSO, revealing mild self-aldol condensation phenomena and potential applications in nanomaterial synthesis.

This study investigates the uptake and retention of stable fluorescent organosilica nanoparticles by macrophages, which play a vital role in scavenging environmental nanoparticles and nanomedicine within the body. We used rhodamine 6G-loaded fluorescent organosilica nanoparticles (SiNP-R6G) synthesized from a thiol-functionalized organosilane precursor. Our primary objective was to establish a quantitative relationship between fluorescent measurements and nanoparticle tracking analysis, enabling the precise “counting” of nanoparticles taken up by macrophages under kinetic measurement conditions. Our kinetic study demonstrated a concentration-dependent, saturable internalization of nanoparticles in a model macrophage (RAW 264.7 cells), with a maximum uptake rate ( V _max ) of 7.9 × 10 ⁴ nanoparticles per hour per cell. The estimated number concentration of nanoparticles for half-maximum uptake was approximately 0.8 trillion nanoparticles per milliliter, and a significant portion (∼80%) of internalized SiNP-R6G remained entrapped within the cells for 48 hours, indicating the sustained particle retention capacity of macrophages. These findings highlight the successful development of a methodology to accurately “count” the cellular uptake of nanoparticles in macrophages, providing valuable insights into the kinetics and retention capabilities of macrophages for nanoparticles.