Capillary Osmosis in a Charged Nanopore Connecting Two Large Reservoirs

Experimental evidence revealed that the performance of nanopore-based biosensing devices can be improved by applying a salt concentration gradient. To provide a theoretical explanation for this observation and explore the mechanisms involved, we model the capillary osmosis (or diffusioosmosis) in a charged solid-state nanopore connecting two large reservoirs. The effects of nanopore geometry and the reservoir salt concentrations are examined. We show that the capillary osmotic flow is from the high salt concentration reservoir to the low salt concentration one, and its magnitude has a maximum as the reservoir salt concentrations vary. In general, the shorter the nanopore and/or the smaller its radius, the faster the osmotic flow. This flow enhances the current recognition, and the ion concentration polarization across nanopore openings raises the entity capture rate, thereby being capable of improving the performance of electrophoresis-based biosensors. The results gathered provide necessary information for designing nanopore-based biosensor devices

Importance of Ionic Polarization Effect on the Electrophoretic Behavior of Polyelectrolyte Nanoparticles in Aqueous Electrolyte Solutions

The electrophoresis of a polyelectrolyte, an entirely porous, charged nanoparticle, in various types of aqueous electrolyte solution is modeled taking account of the presence of multiple ionic species, and its applicability is verified by the experimental data of succinoglycan in the literature. We show that, in addition to the electroosmotic flow around a polyelectrolyte, two types of competing polarization effect are also significant: counterion polarization and co-ion polarization, both of them depend largely on the thickness of the double layer. The presence of these two polarization effects yields profound and interesting electrophoretic behaviors that are distinct to polyelectrolytes. The results gathered provide necessary theoretical background for the interpretation of various types of electrophoresis data in practice. Typical examples include that of a nanopore-based sensing device used, for instance, in DNA sequencing

Targeting Tumor Associated Phosphatidylserine with New Zinc Dipicolylamine-Based Drug Conjugates

A series of zinc­(II) dipicolylamine (ZnDPA)-based drug conjugates have been synthesized to probe the potential of phosphatidylserine (PS) as a new antigen for small molecule drug conjugate (SMDC) development. Using <i>in vitro</i> cytotoxicity and plasma stability studies, PS-binding assay, <i>in vivo</i> pharmacokinetic studies, and maximum tolerated dose profiles, we provided a roadmap and the key parameters required for the development of the ZnDPA based drug conjugate. In particular, conjugate <b>24</b> induced tumor regression in the COLO 205 xenograft model and exhibited a more potent antitumor effect with a 70% reduction of cytotoxic payload compared to that of the marketed irinotecan when dosed at the same regimen. In addition to the validation of PS as an effective pharmacodelivery target for SMDC, our work also provided the foundation that, if applicable, a variety of therapeutic agents could be conjugated in the same manner to treat other PS-associated diseases