The stability of polymeric nanoparticles in serum is critical to their use in drug delivery where dilution after intravenous injection often results in nanoparticle disassembly and drug unloading; however, few investigate this in biologically relevant media. To gain greater insight into nanoparticle stability in blood, the stability of self-assembled polymeric micelles of poly(d,l-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-g-poly(ethylene glycol), P(LA-co-TMCC)-g-PEG, were tested in both serum and individual serum protein solutions. By encapsulating Förster resonance energy transfer pairs and following their release by fluorescence, these micelles demonstrated excellent thermodynamic and kinetic stability in the presence of serum. Further analyses by fast protein liquid chromatography and dynamic light scattering confirmed these data. Moreover, these micelles are compatible with red blood cells, as shown by a hemolysis assay. The stability and compatibility demonstrated in blood suggest that these micelles may be stable in vivo, which is critical for intravenous drug delivery applications. This comprehensive approach to understanding micelle stability and compatibility is broadly applicable.

Nucleation has been generally acknowledged as a rapid but uncontrollable process that is difficult to decouple from the subsequent growth phase. Here, we report our finding that nucleation of semiconductor magic-size clusters (MSCs) can be well-regulated, without a subsequent evolution in size. Colloidal semiconductor CdS MSCs were synthesized by a two-step approach intentionally designed, without the simultaneous formation of nanocrystals of other sizes. The nuclei MSCs exhibit a sharp optical absorption peaking at 311 nm and are thus denoted by MSC−311. We prepared the immediate precursor for MSC−311 denoted by IP311 which is liquid-like, through a reaction which was normally performed to grow CdS conventional quantum dots (QDs), but at a different temperature (180°C) prior to the nucleation and growth of CdS QDs. We demonstrate that the nucleation of MSC−311 from IP311 followed first order kinetics remarkably well, and the presence of a small amount of methanol accelerated this process effectively. Moreover, the liquid-like prenucleation cluster IP311 and the nuclei MSC−311 have similar masses. Accordingly, we propose that the intramolecular reorganization of IP311 results in the nuclei MSC−311, the formation of which features a two-step nucleation pathway. The present study introduces methodology via absorption spectroscopy to monitor the nucleation kinetics of semiconductor MSCs from their immediate precursors. The repeatable, predictable, and controllable nucleation process investigated here brings a deeper insight into nucleation of other semiconductor nanocrystals and contributes to the foundation for the future development of advanced theoretical models for crystal nucleation.

Phosphoenolpyruvate (PEP) is an important precursor for anaerobic production of succinate and malate. Although inactivating PEP/carbohydrate phosphotransferase systems (PTS) could increase PEP supply, the resulting strain had a low glucose utilization rate. In order to improve anaerobic glucose utilization rate for efficient production of succinate and malate, combinatorial modulation of galactose permease (galP) and glucokinase (glk) gene expression was carried out in chromosome of an Escherichia coli strain with inactivated PTS. Libraries of artificial regulatory parts, including promoter and messenger RNA stabilizing region (mRS), were firstly constructed in front of β-galactosidase gene (lacZ) in E. coli chromosome through λ-Red recombination. Most regulatory parts selected from mRS library had constitutive strengths under different cultivation conditions. A convenient one-step recombination method was then used to modulate galP and glk gene expression with different regulatory parts. Glucose utilization rates of strains modulated with either galP or glk all increased, and the rates had a positive relation with expression strength of both genes. Combinatorial modulation had a synergistic effect on glucose utilization rate. The highest rate (1.64 g/L h) was tenfold higher than PTS(-) strain and 39% higher than the wild-type E. coli. These modulated strains could be used for efficient anaerobic production of succinate and malate.