Porins form aqueous channels that aid the diffusion of small hydrophilic molecules across the outer membrane of Gram-negative bacteria. The crystal structures of matrix porin and phosphoporin both reveal trimers of identical subunits, each subunit consisting of a 16-stranded anti-parallel beta-barrel containing a pore. A long loop inside the barrel contributes to a constriction of the channel where the charge distribution affects ion selectivity. The structures explain at the molecular level functional characteristics and their alterations by known mutations.

Enabled by their size and supramolecular structures, nanoparticles (that is, particles of approximately 10 to 100 nanometers) promise to be particularly capable agents in the detection, diagnosis, and treatment of cancer. When loaded with chemotherapeutic agents, nanoparticle delivery to cancerous tissues relative to healthy tissues may be favorably biased by size and through the attachment of targeting ligands to the surface of the particle. Nanoparticles may be made from a variety of materials, and in addition to chemotherapeutic payloads, nanoparticles can incorporate non-bioactive elements useful as diagnostic and device agents. For example, the inclusion of iron oxide colloids enables nanoparticle use as magnetic resonance imaging (MRI) contrast agents, and also, through the application of an alternating magnetic field (AMF), enables the particle to generate enough heat to be used for hyperthermic therapeutic applications. In this report, we also introduce novel Magnetic Nanoparticle Hydro-Gel (MagNaGel TM ) materials comprised of chemotherapeutic agents, iron oxide colloids, and targeting ligands. MagNaGel particles were fabricated in the 20-to 40-nm size range with very narrow size dispersion. These particles demonstrate high (410 wt %) chemotherapeutic loading, tumor-associated biomolecular binding, good magnetic susceptibility, and attractive toxicity and circulation profiles in mouse models. Looking forward, the convergence of drug and device on the nano-scale promises treatment modalities that cannot be practiced through traditionally distinct drug and device combinations. MagNaGel nanoparticles are drug-device hybrids that, when used in conjunction with diagnostic MRI and inductive heating, may play a key role in new and powerful cancer treatment regimens. Drug Dev. Res. 67:70-93, 2006.

When purified without the use of ionic detergents, both OmpA and OprF proteins contained nearly 20% ␣-helical structures, which disappeared completely upon the addition of sodium dodecyl sulfate. This result suggests that the proteins fold in a similar manner, with an N-terminal, membrane-spanning ␤-barrel domain and a C-terminal, globular, periplasmic domain.OmpA is one of the major outer membrane proteins of Escherichia coli. It appears to exist as a monomer, and it shows very little pore-forming activity (16), apparently because only a small fraction of the OmpA population contains open channels (17). The accepted folding model of OmpA contains an Nterminal domain (residues 1 to 170) consisting of eight antiparallel ␤-strands, as well as a periplasmic C-terminal domain (residues 196 to 325) (8, 12). The two domains are connected by an Ala-Pro-rich hinge sequence. The proposed structure of the N-terminal domain is supported by a wealth of data, including data indicating the localization of phage-binding sites exclusively on segments predicted to correspond to the external loops connecting ␤-strands (8) and Raman spectroscopy data (19). However, the secondary structure of the C-terminal domain has so far received little attention.Pseudomonas aeruginosa outer membrane contains OprF as a major protein. It is a homolog of E. coli OmpA (2) and similarly produces diffusion pores of low permeability (5,9,20). In contrast to OmpA, however, the entire length of OprF has been proposed to traverse the outer membrane as 18 ␤-strands (11).We studied the secondary structure of these proteins, which were purified in the total absence of denaturing, ionic detergents, in view of these conflicting models of folding. OmpA was purified as follows. Cell envelope fraction from a 4-liter culture of HN705 (⌬ompC ompF::Tn5) (16) was first extracted twice with 50-ml portions of 20 mM N-2-hydroxyethylpiperazine-NЈ-2-ethanesulfonic acid (HEPES)-Na buffer (pH 7.5)-3% octylpolyoxyethylene (POE) (Alexis Biochemicals, San Diego, Calif.) (10) and then extracted once with 50 ml of the same solution containing 1 M NaCl in addition to solubilize most of the cytoplasmic membrane proteins. The residue was then extracted with 20 ml of 20 mM HEPES buffer-10% octyl-POE-1 M NaCl, and the extract was fractionated by gel filtration on a column (1.5 by 92 cm) of Toyo Pearl 50F (TosoHaas, Montgomeryville, Pa.), equilibrated, and eluted with 0.1% dodecyl maltoside-0.4 M NaCl-10 mM HEPES buffer-3 mM NaN 3 . When the circular dichroism (CD) spectrum was taken on a sample concentrated by ultrafiltration through an Amicon (Beverly, Mass.) PM-10 filter, it showed a strong ellipticity with two minima at 209 and 222 nm, characteristic of structures containing a significant fraction of ␣-helix. When curve fitting was used to estimate the secondary structure (1), OmpA appeared to contain 18% ␣-helix, 40% ␤-strand, 5% ␤-turn, and 25% unordered structure (Fig. 1). In contrast, OmpA prepared by solubilization of the outer membrane by sodium dodecyl sulfate (SDS) (16) ...

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