Asymchem Life Science Tianjin Co. Ltd.

Calcium overload-mediated tumor treatment conventionally necessitates calcium-containing drugs. However, these drugs are susceptible to calcium ion leakage during in vivo delivery, potentially causing adverse effects such as hypercalcemia and hypertension. Furthermore, voltage-gated ion channels (VGICs) on the tumor cell membrane stringently regulate calcium ion influx to preserve intracellular calcium homeostasis. To address these issues, a calcium-free piezoelectric nanogenerator, (K, Na) NbO₃ (KNN), capable of local and wireless discharge (at a voltage of up to 0.4 mV) into tumors under ultrasound (US) excitation, is designed to open VGICs. Given the significantly higher extracellular calcium ion concentration compared to intracellular levels (approximately 15,000-fold), a substantial influx of calcium ions ensures, leading to intracellular calcium overload. Concurrently, US stimulates KNN to undergo piezoelectric catalysis, converting water into reactive oxygen species (ROS). The synergistic effect of calcium overload and high ROS oxidation induces mitochondrial damage, culminating in tumor elimination. Additionally, the calcium ion influx induces polarization of tumor-associated macrophages from an immunosuppressive M2 phenotype to an immunity-promoting M1 phenotype, thereby enhancing systemic anti-tumor immune responses. This study demonstrates that local electric field within tumors can open VGICs for efficient and safe calcium overload-mediated tumor treatment, showing great potential for clinical translation.

Oxaprozin (OXP), a commonly utilized non-steroidal anti-inflammatory drug, exhibits limited water solubility that diminishes its therapeutic efficacy.In this study, seven new OXP multicomponent crystals were successfully prepared through a multicomponent crystal strategy, including one OXP-MIN (Minoxidil) drug-drug cocrystal, one OXP-ADMP cocrystal, two OXP anionic salts (OXP-3HYP salt and OXP-3AP salt), and three OXP cationic salts (OXP-BSA salt, OXP-PTSA-ACN salt solvate, and OXP-PCBSA-ACN salt solvate).Among them, the OXP-ADMP cocrystal, OXP-3HYP salt, and OXP-3AP salt significantly improved the dissolution performance of OXP.By combining the calculations of solvation free energy and lattice energy, the intrinsic mechanism of solubilization was revealed.Initially, the hydrogen bonding sites of OXP were determined through Full Interaction Maps (FIM) anal., and 54 coformers from different categories were selected for computational and exptl. screening.Liquid-assisted grinding experiments successfully yielded 23 new OXP-based phases, and the combination of the Conductor-like Screening Model for Real Solvents (COSMO-RS) and the Mol. Complementarity (MC) method increased the computational screening success rate to 83.3%.The crystal structures of seven new OXP multicomponent crystals were structurally characterized through single crystal X-ray diffraction (SCXRD).Accelerated stability tests indicated that all multicomponent crystals exhibited excellent phase stability, providing strong support for maintaining drug efficacy and safety.Solubility and dissolution tests revealed that OXP-ADMP cocrystal, OXP-3HYP salt, and OXP-3AP salt significantly improved the solubility (by 14.66, 11.78, and 14.66%, resp.) and dissolution rate (by 3.35, 21.79, and 44.69%, resp.) of OXP in pH 6.8 buffer.Notably, the OXP-MIN drug-drug cocrystal substantially reduced the solubility (by 86.06%) and dissolution rate (by 92.20%) of MIN under the same conditions, highlighting its potential for achieving sustained release of MIN and offering a promising strategy for low-dose oral MIN treatment of alopecia.Conformational similarity anal. showed that salt formation induced more significant conformational changes in OXP mols. compared to cocrystal formation.The formation mechanisms of cocrystals, anionic salts, and cationic salts, as well as the stoichiometric ratio differences between OXP and coformers in multicomponent crystals, were elucidated through pKa and Mol. Electrostatic Potential Surface (MEPS) anal.Furthermore, the strength of intermol. hydrogen bonds was evaluated using Independent Gradient Model anal. based on Hirshfeld Surfaces (IGMH) and Atoms in Mols. (AIM) anal.This study not only provides critical theor. perspectives for improving drug solubility through crystal engineering techniques but also presents a new case for the development of drug-drug cocrystals.

With the continuous advancement of nanotechnol., nanofluid flooding has become a widely adopted method in the development of oil and gas fields, recognized for its economic viability and efficiency in oil displacement.However, challenges remain regarding nano-oil displacement materials, including low interfacial activity and an ambiguous interfacial mechanism.Therefore, it is crucial to construct nanomaterials with high interfacial activity and investigate their interfacial mechanisms.In this study, we successfully constructed functionalized MoS₂ nanosheets characterized by high interfacial activity (SDS-MoS₂).The SDS-MoS₂ nanosheets exhibited superior interfacial properties, emulsification capabilities, climbing film effects, and oil displacement efficiencies.When a dispersion of the nanosheets at a concentration of 0.01 wt % is injected at 3 pore volumes (PV), the enhanced oil recovery can achieve 18.05%.Based on these findings, the interfacial interaction mechanism of SDS-MoS₂ nanosheets was elucidated through microscopic visual displacement experimentsThis research aims to provide theor. insights into synthesizing high interfacial activity nano-oil displacement materials, analyzing their oil-water interface mechanisms, and advancing the practical application of these materials in oilfield settings.