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Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability, and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma (HCC) exhibit a 10,000-fold greater affinity for HCC than for hepatocytes, endothelial cells, and immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, siRNA, and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer allow a single protocell loaded with a drug cocktail to kill a drug-resistant HCC cell, representing a 106-fold improvement over comparable liposomes.

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A semitheoretical formalism based on classical electromagnetic wave theory has been developed for application to the quantitative treatment of reflection spectra from multilayered anisotropic films on both metallic and nonmetallic substrates. Both internal and external reflection experiments as well as transmission can be handled. The theory is valid for all wavelengths and is appropriate, therefore, for such experiments as x-ray reflectivity, uv–visible spectroscopic ellipsometry, and infrared reflection spectroscopy. Further, the theory is applicable to multilayered film structures of variable number of layers, each with any degree of anisotropy up to and including full biaxial symmetry. The reflectivities (and transmissivities) are obtained at each frequency by solving the wave propagation equations using a rigorous 4×4 transfer matrix method developed by Yeh in which the optical functions of each medium are described in the form of second rank (3×3) tensors. In order to obtain optical tensors for materials not readily available in single crystal form, a method has been developed to evaluate tensor elements from the complex scalar optical functions (n̂) obtained from the isotropic material with the limitations that the molecular excitations are well characterized and obey photon–dipole selection rules. This method is intended primarily for infrared vibrational spectroscopy and involves quantitative decomposition of the isotropic imaginary optical function (k) spectrum into a sum of contributions from fundamental modes, the assignment of a direction in molecular coordinates to the transition dipole matrix elements for each mode, the appropriate scaling of each k vector component in surface coordinates according to a selected surface orientation of the molecule to give a diagonal im(n̂) tensor, and the calculation of the real(n̂) spectrum tensor elements by the Kramers–Kronig transformation. Tensors for other surface orientations are generated by an appropriate rotation matrix operation. To test the viability of this approach, three sets of experimentally derived infrared spectra of oriented monolayer assemblies on quite distinctively different substrates were chosen for simulation: (1) n-alkanethiols self- assembled onto gold, (2) n-alkanoic acid salt Langmuir–Blodgett (LB) monolayers on carbon, and (3) n-alkanoic acid salt LB monolayers on silica glass. The formalism developed was used to simulate the spectral response and to derive structural features of the monolayers. Good agreement was found where comparisons with independent studies could be made and, in general, the method appears quite useful for structural studies of highly organized thin films.

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Formation of a new class of layered, microcrystalline polymers from a simple hydrolytic polycondensation of n-alkyltrichlorosilanes in water is demonstrated. The structure of the polymeric condensate, determined from a combination of spectroscopic, diffraction, and thermal analysis techniques, consists of highly uniform, pillared microcrystallites in which the inorganic siloxy backbones are present in periodic layers, each containing a monomolecular layer of intercalated water, separated by crystalline assemblies of alkyl chains. The alkyl-chain organization shows a remarkable resemblance to that in highly organized, self-assembled monolayers formed from the precursor silane molecules on hydrophilic substrates and this parallel lends support to the critical importance of water in monolayer self-assembly of silanes.

We describe a method for direct, quantitative, in vivo lipid profiling of oil-producing microalgae using single-cell laser-trapping Raman spectroscopy. This approach is demonstrated in the quantitative determination of the degree of unsaturation and transition temperatures of constituent lipids within microalgae. These properties are important markers for determining engine compatibility and performance metrics of algal biodiesel. We show that these factors can be directly measured from a single living microalgal cell held in place with an optical trap while simultaneously collecting Raman data. Cellular response to different growth conditions is monitored in real time. Our approach circumvents the need for lipid extraction and analysis that is both slow and invasive. Furthermore, this technique yields real-time chemical information in a label-free manner, thus eliminating the limitations of impermeability, toxicity, and specificity of the fluorescent probes common in currently used protocols. Although the single-cell Raman spectroscopy demonstrated here is focused on the study of the microalgal lipids with biofuel applications, the analytical capability and quantitation algorithms demonstrated are applicable to many different organisms and should prove useful for a diverse range of applications in lipidomics.lipid analysis | bioenergy T he global concerns surrounding unabated fossil fuel consumption and the risk of significant environmental impact caused by the associated greenhouse gas emissions, compounded by potential challenges associated with land-based biofuels, have renewed significant interest in microalgae as an alternative feedstock for the production of biodiesel and other biofuels (1). Microalgae hold considerable promise because of their ability to synthesize and store lipids, such as fatty acids and triacylglycerols (TAGs), which can be readily converted into biodiesel (fatty acid methyl or ethyl esters) through relatively simple chemical reactions (2). Small yet efficient, microalgae are attractive for many reasons, including their rapid, cost-effective, and resource-efficient production on nonarable land or photobioreactors (3), with impaired water, and for especially significant lipid production-up to 20-50% of their total dry weight, with examples of up to 80% under certain conditions reported (4). It has been estimated that lipid production of microalgae could be 30 times more efficient in terms of relative production of lipids per acre per year than any other terrestrial plant oil feedstock (2, 5).Under optimal growth conditions, microalgae synthesize fatty acids in the form of various glycerol-based membrane lipids primarily for structural and functional roles (6). In contrast, adverse environmental or metabolic stress conditions such as nutrient limitation, commonly referred to as "lipid trigger" conditions, result in an increase in carbon partitioning and accumulation of substantial proportions of neutral lipids (20-50% of dry weight), primarily in the form of TAGs. The TAGs are a form of...