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In the present work, high-performance mixed matrix membranes containing amines have been developed for effective CO 2 removal at high pressures (15-28 bar) and high temperatures (103-121 °C). The membrane was synthesized by compatibly embedding amino-functionalized multi-walled carbon nanotubes (AF-MWNTs) as mechanical reinforcing fillers in the crosslinked polyvinylalcohol-polysiloxane/amine blend. The surface functionalization of MWNTs allows strong coupling with the hydrophilic membrane matrix to form a nano-reinforced facilitated transport membrane, which achieved exceptional CO 2 selectivity and permeability via the facilitated transport mechanism as well as attractive membrane stability via the incorporation of MWNTs. The synthesized membranes exhibited an average CO 2 permeability of 957 Barrers coupled with high selectivities vs. H 2 (56), CH 4 (264), and N 2 (384) at 107 °C and 15 bar. The effects of AF-MWNT loading, high molecular weight species content, selective layer thickness, feed pressure, relative humidity, and temperature on membrane performance were thoroughly studied for a fundamental understanding of membrane properties. Furthermore, a mathematical model has been used to describe and explain the thickness-dependent CO 2 transport behavior in the membrane. The combination of high CO 2 permeability and good selectivities vs. CH 4 , H 2 , and N 2 , along with enhanced mechanical stability, makes the membrane a promising candidate for the gas separation applications at high pressures.

A subtle but highly pertinent factor in the self-assembly of hierarchical nanostructures is the kinetic landscape. Self-assembly of a hierarchical multicomponent system requires the intricate balance of noncovalent interactions on a similar energy scale that can result in several self-assembly processes occurring at different time scales. We seek to understand the hierarchical assemblies within an amphiphilic 3-helix peptide-PEG-lipid conjugate system in the formation process of highly stable 3-helix micelles (3HMs). 3HM self-assembles through multiple parallel processes: helix folding, coiled-coil formation, micelle assembly, and packing of alkyl chains. Our results show that the kinetic pathway of 3HM formation is mainly governed by two confounding factors: lateral diffusion of amphiphiles to form coiled-coils within the micelle corona and packing of alkyl tails within the hydrophobic micelle core. 3HM has exhibited highly desirable attributes as a drug delivery nanocarrier; understanding the role of individual components in the kinetic pathway of 3HM formation will allow us to exert better control over the kinetic pathway, as well as to enhance future design and eventually manipulate the kinetic intermediates for potential drug delivery applications.

Ligand-functionalized, multivalent nanoparticles have been extensively studied for biomedical applications from imaging agents to drug delivery vehicles. However, the ligand cluster size is usually heterogeneous and the local valency is ill-defined. Here, we present a mixed micelle platform hierarchically self-assembled from a mixture of two amphiphilic 3-helix and 4-helix peptide-polyethylene glycol (PEG)-lipid hybrid conjugates. We demonstrate that the local multivalent ligand cluster size on the micelle surface can be controlled based on the coiled-coil oligomeric state. The oligomeric states of mixed peptide bundles were found to be in their individual native states. Similarly, mixed micelles indicate the orthogonal self-association of coiled-coil amphiphiles. Using differential scanning calorimetry, fluorescence recovery spectroscopy, and coarse-grained molecular dynamics simulation, we studied the distribution of coiled-coil bundles within the mixed micelles and observed migration of coiled-coils into nanodomains within the sub-20 nm mixed micelle. This report provides important insights into the assembly and formation of nanophase-separated micelles with precise control over the local multivalent state of ligands on the micelle surface.

Understanding the complex interplay of factors affecting nanoparticle accumulation in solid tumors is a challenge that must be surmounted to develop effective cancer nanomedicine. Among other unique microenvironment properties, tumor vascular permeability is an important feature of leaky tumor vessels which enables nanoparticles to extravasate. However, permeability has thus far been measured by intravital microscopy on optical window tumors, which has many limitations of its own. Additionally, mathematical models of particle tumor transport are often too complicated to be accessible to most researchers. Here, we present a more simplified and accessible mathematical model based on diffusive flux, which uses particle tumor accumulation and plasma pharmacokinetics to yield effective permeability, P eff. This model, called diffusive flux modeling (DFM), allows effects from multiple parameters to be decoupled and is also the first demonstration, to the best our knowledge, of extracting P eff values from bulk biodistribution results (e.g., routine positron emission tomography studies). The DFM equation was used to explain in vivo results of sub-20 nm nanocarriers called three-helix-micelles (3HM), particularly 3HM’s selective accumulation in different tumor models. When DFM was applied to multiple published biodistribution data, a semiquantitative comparison of various tumor models, particle size, and active targeting strategies could be made. The analysis clearly pointed out the importance of balancing multiple characteristics of nanoparticles to ensure successful treatment outcome and highlights the usefulness of this simple model for initial particle design, selection, and subsequent optimization.