Determination of Pore Sizes and Relative Porosity in Porous Nanoshell Architectures Using Dextran Retention with Single Monomer Resolution and Proton Permeation

Abstract

Unilamellar phospholipid vesicles prepared using the polymerizable lipid bis-sorbylphosphatidylcholine (bis-SorbPC) yield three-dimensional nanoarchitectures that are highly permeable to small molecules. The resulting porous phospholipid nanoshells (PPNs) are potentially useful for a range of biomedical applications including nanosensors and nanodelivery vehicles for cellular assays and manipulations. The uniformity and size distribution of the pores, key properties for sensor design and utilization, has not previously been reported. Fluorophore-assisted carbohydrate electrophoresis (FACE) was utilized to assess the nominal molecular weight cutoff limit (NMCL) of the PPN via analysis of retained dextran with single monomer resolution. The NMCL of PPNs prepared from pure bis-SorbPC was equivalent to a 1800 Da linear dextran, corresponding to a maximum pore diameter of 2.6 nm. Further investigation of PPNs prepared using binary mixtures of bis-SorbPC and dioleylphosphatidylcholine (DOPC) revealed a similar NMCL when the bis-SorbPC content exceeded 30 mol %, whereas different size-dependent permeation was observed below this composition. Below 30 mol % bis-SorbPC, dextran retention provided insufficient mass resolution (162 Da) to observe porosity on the experimental time scale; however, proton permeability showed a marked enhancement for bis-SorbPC ≥ 10 mol %. Combined these data suggest that the NMCL for native pores in bis-SorbPC PPNs results from an inherent property within the lipid assembly that can be partially disrupted by dilution of bis-SorbPC below a critical value for domain formation. Additionally, the analytical method described herein should prove useful for the challenging task of elucidating porosity in a range of three-dimensional nanomaterials.

Aptamer-functionalized porous phospholipid nanoshells for direct measurement of Hg2+ in urine

“…To enhance the stability of the aptamer sensor in biological fluids, we encapsulated the aptamer within a PPN. PPNs are water-filled nanoshells that have an inherent porosity within the nanoshell membrane [34;38]. Prior work has shown that PPNs retain compounds greater than 3 kDa for an indefinite time frame, yet allow unimpeded access of compounds less than 1.5 kDa, irrespective of charge [34;38].…”

“…The experiment was performed at 25 (±1) ° C in a refractive index matching solution. Prior works have shown that PPNs retain material with MW larger than the cutoff for indefinite time frames [34;38]. …”

“…5 nm) membrane, and an interior environment with minimal diffusional impediments. Furthermore, unlike traditional phospholipid liposomes, PPNs present a surface with a size-dependent and charge-independent mass transport across the membrane, functioning similarly to a dialysis membrane [34;38]. The molecular weight cutoff of the PPN is ca.…”

“…2,000 Da thus allowing small molecule analytes to readily diffuse across the membrane while at the same time impeding the transport of large molecular weight species, e.g. proteins and enzymes [34;38]. The net result is an environment that facilitates diffusion limited mass transport across the membrane, yet protects the interior cargo from degradation by large molecular weight external components.…”

Structures and Synthesis of Zwitterionic Polymers

“…In fact, it seems that nearly the full spectrum of polymerizable groups suited for radical polymerization has been used to make polyzwitterions in the past, including not only styrenes, vinylpyridines, vinylimidazoles or vinylesters [124], but also rather uncommon polymerizable groups such as dienoic acids [123,124,[131][132][133][134][135][136][137][138][139], vinylcyclopropanes [124,134] or isocyanides [69], and cyclopolymerizing species such as diallylammonium [64,87,88,124,134,[140][141][142][143][144][145][146][147][148][149][150][151][152][153] and closely related divinyl monomers [93,94]. Moreover, a number of monomers confined exclusively to (often alternating) radical copolymerization, such as vinylethers [124,134], fumarates and maleates [124,134,[154][155][156], isobutylenes [157] and ...…”