Highly Stable, Ultrasmall Polymer-Grafted Nanobins (usPGNs) with Stimuli-Responsive Capability.

Highly stable and stimuli/pH-responsive ultrasmall polymer-grafted nanobins (usPGNs) have been developed by grafting a small amount (10 mol %) of short (4.3 kDa) cholesterol-terminated poly(acrylic acid) (Chol-PAA) into an ultrasmall unilamellar vesicle (uSUV). The usPGNs are stable against fusion and aggregation over several weeks, exhibiting over 10-fold enhanced cargo retention in biologically relevant media at pH 7.4 in comparison with the parent uSUV template. Coarse-grained molecular dynamics (CGMD) simulations confirm that the presence of the cholesterol moiety can greatly stabilize the lipid bilayer. They also show extended PAA chain conformations that can be interpreted as causing repulsion between colloidal particles, thus stabilizing them against fusion. Notably, CGMD predicted a clustering of the Chol-PAA chains on the lipid bilayer under acidic conditions due to intra- and interchain hydrogen bonding, leading to the destabilization of local membrane areas. This explains the experimental observation that usPGNs can be triggered to release a significant amount of cargo upon acidification to pH 5. These developments put the lipid-bilayer-embedded Chol-PAA in stark contrast with traditional poly(acrylic acid) systems where the molar mass (Mn) of the polymer chains must exceed 16.5 kDa to achieve stimuli-responsive changes in conformation. They also distinguish the small usPGNs from the much-larger polymer-caged nanobin platform where the Chol-PAA chains must be covalently cross-linked to engender stimuli-responsive behaviors.

Acid-degradable polymer-caged lipoplex (PCL) platform for siRNA delivery: facile cellular triggered release of siRNA.

An acid-degradable polymer-caged lipoplex (PCL) platform consisting of a cationic lipoplex core and a biocompatible, pH-responsive polymer shell has been developed for the effective delivery of small interfering RNA (siRNA) through a combination of facile loading, rapid acid-triggered release, cellular internalization, and effective endosomal escape. In vitro testing of this degradable PCL delivery platform reveals ∼45- and ∼2.5-fold enhancement of enhanced green fluorescent protein knockdown in cancer cells in comparison to either free siRNA or siRNA-loaded non-acid-degradable lipoplex formulations, respectively.

The role of viscosity on polymer ink transport in dip-pen nanolithography.

Understanding how ink transfers to a surface in dip-pen nanolithography (DPN) is crucial for designing new ink materials and developing the processes to pattern them. Herein, we investigate the transport of block copolymer inks with varying viscosities, from an atomic force microscope (AFM) tip to a substrate. The size of the patterned block copolymer features was determined to increase with dwell time and decrease with ink viscosity. A mass transfer model is proposed to describe this behaviour, which is fundamentally different from small molecule transport mechanisms due to entanglement of the polymeric chains. The fundamental understanding developed here provides mechanistic insight into the transport of large polymer molecules, and highlights the importance of ink viscosity in controlling the DPN process. Given the ubiquity of polymeric materials in semiconducting nanofabrication, organic electronics, and bioengineering applications, this study could provide an avenue for DPN to expand its role in these fields.

pH-Responsive Theranostic Polymer-Caged Nanobins (PCNs): Enhanced Cytotoxicity and T1 MRI Contrast by Her2-Targeting.

A PCN theranostic platform comprises a doxorubicin (DXR)-loaded liposomal core and an acid-sensitive polymer shell that is functionalized with Herceptin and GdIII-based MRI contrast agents. In vitro testing reveals a 14-fold increase in DXR-based cytotoxicity versus a non-targeted analogue and an 120-fold improvement in cellular GdIII-uptake in comparison with clinically approved DOTA-GdIII, leading to significant T1 MRI contrast enhancement.

Multigram Synthesis of a Chiral Substituted Indoline Via Copper-Catalyzed Alkene Aminooxygenation.

(S)-5-Fluoro-2-(2,2,6,6-tetramethylpiperidin-1-yloxymethyl)-1-tosylindoline, a 2-methyleneoxy-substituted chiral indoline, was synthesized on multigram scale using an efficient copper-catalyzed enantioselective intramolecular alkene aminooxygenation. The synthesis is accomplished in four steps and the indoline is obtained in 89% ee (>98% after one recrystallization). Other highlights include efficient gram-scale synthesis of the (4R,5S)-di-Ph-box ligand and efficient separation of a monoallylaniline from its bis(allyl)aniline by-product by distillation under reduced pressure.