Biocompatible Snowman-like Dimer Nanoparticles for Improved Cellular Uptake in Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is one of the most aggressive types of human cancers. Although paclitaxel (PTX) was proven to exert potent anti-tumor effects against ICC, the delivery of PTX is still challenging due to its hydrophobic property. Nanoparticle (NP)-based carriers have been proven to be effective drug delivery vehicles. Among their physicochemical properties, the shape of NPs plays a crucial role in their performance of cellular internalization and thus anti-tumor efficacy of loaded drugs. In this study, dumbbell-like and snowman-like dimer NPs, composed of a polylactic acid (PLA) bulb and a shellac bulb, were designed and prepared as drug nanocarriers to enhance the efficiency of cellular uptake and anti-tumor performance. PLA/shellac dimer NPs prepared through rapid solvent exchange and controlled co-precipitation are biocompatible and their shape could flexibly be tuned by adjusting the concentration ratio of shellac to PLA. Drug-loaded snowman-like PLA/shellac dimer NPs with a sharp shape exhibit the highest cellular uptake and best cell-killing ability against cancer cells in an in vitro ICC model over traditional spherical NPs and dumbbell-like dimer NPs, as proven with the measurements of flow cytometry, fluorescent confocal microscopy, and the CCK8 assay. The underlying mechanism may be attributed to the lower surface energy required for the smaller bulbs of snowman-like PLA/shellac dimer NPs to make the initial contact with the cell membrane, which facilitates the subsequent penetration through the cellular membrane. Therefore, these dimer NPs provide a versatile platform to tune the shape of NPs and develop innovative drug nanocarriers that hold great promise to enhance cellular uptake and therapeutic efficacy

Mineral precipitation kinetics : assessing the effect of hydrostatic pressure and its implication on the nucleation mechanism

Sulfate minerals (barite, anhydrite, and celestite) can be a technological hindrance as a result of scale formation especially for operations where seawater injection is involved. The effect of pH, temperature, and saturation index (SI) on sulfate mineral nucleation and growth are fairly well-known, but the influence of pressure on the nucleation kinetics has attracted no attention. Here we show that nucleation kinetics of barite, anhydrite, and celestite is highly dependent on hydrostatic pressure applied even under constant thermodynamic driving force, that is, at the same supersaturation level. Activation parameters of barite nucleation kinetics were calculated, and measured values are in agreement with literature. The negative activation volume measured suggests that barite nucleation from hydrated Ba²⁺ and SO₄^2– ions is coupled to an overall volume decrease, albeit a large volume increase due to dehydration is expected. The results indicate that nucleation is not controlled by desolvation of solvated precursor Ba²⁺ and SO₄^2– ions but rather by an intrinsic volume collapse in the rate-determining step of the nucleation and crystal growth processes. The activation parameters measured in this study indirectly support previous findings of formation of hydrated barite precursor before formation of crystalline barite particles

Development and Application of a New Theoretical Model for Additive Impacts on Mineral Crystallization

Additives play an important role in crystallization controls in both natural and industrial processes. Due to the lack of theoretical understanding of how additives work, the use and design of additives in various disciplines are mostly conducted empirically. This study has developed a new theoretical model to predict the additive impacts on crystallization based on the classical nucleation theory and regular solution theory. The new model assumes that additives can impact the nucleus partial molar volume and the apparent saturation status of the crystallization minerals. These two impacts were parametrized to be proportional to additive concentrations and vary with inhibitors. As a practical example, this new model has been used to predict barite induction times without inhibitors from 4 to 250 °C and in the presence of eight different scale inhibitors from 4 to 90 °C. The predicted induction times showed close agreement with the experimental data published previously or produced in this study. Such agreement indicates that this new theoretical model can be widely adopted in various disciplines to evaluate mineral formation kinetics, elucidate mechanisms of additive impacts, predict minimum effective dosage (MED) of additives, and guide the design of new additives, to mention a few

Calcite and Barite Solubility Measurements in Mixed Electrolyte Solutions and Development of a Comprehensive Model for Water-Mineral-Gas Equilibrium of the Na-K-Mg-Ca-Ba-Sr-Cl-SO₄‑CO₃‑HCO₃‑CO₂(aq)‑H₂O System up to 250 °C and 1500 bar

Calcite and barite are two of the most common scale minerals that occur in various geochemical and industrial processes. Their solubility predictions at extreme conditions (e.g., up to 250 °C and 1500 bar) in the presence of mixed electrolytes are hindered by the lack of experimental data and thermodynamic model. In this study, calcite solubility in the presence of high Na₂SO₄ (i.e., 0.0407 m Na₂SO₄) and barite solubility in a synthetic brine at up to 250 °C and 1500 bar were measured using our high-temperature high-pressure geothermal apparatus. Using this set of experimental data and other thermodynamic data from a thorough literature review, a comprehensive thermodynamic model was developed based on the Pitzer theory. In order to generate a set of Pitzer theory virial coefficients with reliable temperature and pressure dependencies which are applicable to a typical water system (i.e., Na-K-Mg-Ca-Ba-Sr-Cl-SO₄-CO₃-HCO₃-CO₂-H₂O) that may occur in geochemical and industrial processes, we simultaneously fit all available mineral solubility, CO₂ solubility, as well as solution density. With this model, calcite and barite solubilities can be accurately predicted under such extreme conditions in the presence of mixed electrolytes. Furthermore, the 95% confidence intervals of the estimation errors for solution density predictions are within 4 × 10^–4 g/cm³. The relative errors of CO₂ solubility prediction are within 0.75%. The estimation errors of the saturation index mean values for gypsum, anhydrite, and celestite are within ±0.1 and that for halite is within ±0.01, most of which are within experimental uncertainties