Binding of DNA origami to lipids: maximizing yield and switching via strand displacement.

Liposomes are widely used as synthetic analogues of cell membranes and for drug delivery. Lipid-binding DNA nanostructures can modify the shape, porosity and reactivity of liposomes, mediated by cholesterol modifications. DNA nanostructures can also be designed to switch conformations by DNA strand displacement. However, the optimal conditions to facilitate stable, high-yield DNA-lipid binding while allowing controlled switching by strand displacement are not known. Here, we characterized the effect of cholesterol arrangement, DNA structure, buffer and lipid composition on DNA-lipid binding and strand displacement. We observed that binding was inhibited below pH 4, and above 200 mM NaCl or 40 mM MgCl2, was independent of lipid type, and increased with membrane cholesterol content. For simple motifs, binding yield was slightly higher for double-stranded DNA than single-stranded DNA. For larger DNA origami tiles, four to eight cholesterol modifications were optimal, while edge positions and longer spacers increased yield of lipid binding. Strand displacement achieved controlled removal of DNA tiles from membranes, but was inhibited by overhang domains, which are used to prevent cholesterol aggregation. These findings provide design guidelines for integrating strand displacement switching with lipid-binding DNA nanostructures. This paves the way for achieving dynamic control of membrane morphology, enabling broader applications in nanomedicine and biophysics.

Effect of Different Crowding Agents on the Architectural Properties of the Bacterial Nucleoid-Associated Protein HU.

HU is a nucleoid-associated protein expressed in most eubacteria at a high amount of copies (tens of thousands). The protein is believed to bind across the genome to organize and compact the DNA. Most of the studies on HU have been carried out in a simple in vitro system, and to what extent these observations can be extrapolated to a living cell is unclear. In this study, we investigate the DNA binding properties of HU under conditions approximating physiological ones. We report that these properties are influenced by both macromolecular crowding and salt conditions. We use three different crowding agents (blotting grade blocker (BGB), bovine serum albumin (BSA), and polyethylene glycol 8000 (PEG8000)) as well as two different MgCl2 conditions to mimic the intracellular environment. Using tethered particle motion (TPM), we show that the transition between two binding regimes, compaction and extension of the HU protein, is strongly affected by crowding agents. Our observations suggest that magnesium ions enhance the compaction of HU-DNA and suppress filamentation, while BGB and BSA increase the local concentration of the HU protein by more than 4-fold. Moreover, BGB and BSA seem to suppress filament formation. On the other hand, PEG8000 is not a good crowding agent for concentrations above 9% (w/v), because it might interact with DNA, the protein, and/or surfaces. Together, these results reveal a complex interplay between the HU protein and the various crowding agents that should be taken into consideration when using crowding agents to mimic an in vivo system.

Entropic stabilization of folded RNA in crowded solutions measured by SAXS.

Non-coding RNAs must fold into specific structures that are stabilized by metal ions and other co-solutes in the cell's interior. Large crowder molecules such as PEG stabilize a bacterial group I ribozyme so that the RNA folds in low Mg2+ concentrations typical of the cell's interior. To understand the thermodynamic origins of stabilization by crowder molecules, small angle X-ray scattering was used to measure the folding and helix assembly of a bacterial group I ribozyme at different temperatures and in different MgCl2 and polyethylene glycol (PEG) concentrations. The resulting phase diagrams show that perturbations to folding by each variable do not overlap. A favorable enthalpy change drives the formation of compact, native-like structures, but requires Mg2+ ions at all temperatures studied (5-55°C). PEG reduces the entropic cost of helix assembly and increases correlations between RNA segments at all temperatures. The phase diagrams also revealed a semi-compact intermediate between the unfolded and folded ensemble that is locally more flexible than the unfolded state, as judged by SHAPE modification. These results suggest that environmental variables such as temperature and solute density will favor different types of RNA structures.

The influence of hydrogen bonding on the dielectric constant and the piezoelectric energy harvesting performance of hydrated metal salt mediated PVDF films.

Polyvinylidene fluoride (PVDF) films are filled with various mass fractions (wt%) of hydrated metal salt (MgCl2·6H2O) (Mg-salt) to fabricate high performance piezoelectric energy harvesters (PEHs). They deliver up to 4 V of open circuit voltage by simply repeated human finger imparting (under a pressure of ∼4.45 kPa) and also generate sufficient power to turn on at least ten commercial blue light emitting diodes (LEDs) instantly. The enhanced piezo-response is attributed to the combined effect of the change in the inherent dipole moment of the electroactive phase containing PVDF itself and H-bonding arising between the Mg-salt filler and PVDF via electrostatic interactions. Furthermore, it also successfully charged the capacitors, signifying practical applicability as a piezoelectric based energy harvester power source. UV-visible optical absorption spectral analysis revealed the possibility to estimate a change in the optical band gap value at different concentrations of Mg-salt filler added PVDF films that possess a useful methodology where the Mg-salt can be used as an optical probe. In addition dielectric properties have been studied to understand the role of molecular kinetic and interfacial polarization occurs in H-bond PVDF films at different applied frequencies at room temperature.

Physicochemical properties of radiopaque dicalcium silicate cement as a root-end filling material in an acidic environment.

AIM: To investigate the effect of two solutions differing by pH (7.4 and 4.0) on the physicochemical properties of a radiopaque dicalcium silicate cement. METHODOLOGY: The cement was prepared by hand-mixing the dicalcium silicate powder with distilled water in a liquid-to-powder ratio of 0.4 mL g(-1) . A total of 253 cement specimens with dimension of 6 mm (diameter) × 3 mm (height) were used. The morphology, weight loss, porosity and diametral tensile strength of the cement were evaluated after soaking in a solution for different time intervals, in addition to pH changes in the cement-immersed solutions. RESULTS: After soaking in a pH 7.4 solution for 1 day, the particle size of precipitated apatite spherulites on the cement surfaces was greater than that obtained in a pH 4.0 solution. Solution pH did not result in a significant difference (P > 0.05) in diametral tensile strength of cement specimens at the same soaking time-point. On day 30, the sample was associated with a weight loss of 0.8% in a pH 4.0 solution, whereas in a pH 7.4 solution, a weight increase of 0.2% occurred. A greater porosity of the cement soaked in a pH 4.0 was found compared with that in the solution with pH 7.4. Soaking time affected significantly (P < 0.05) the porosity, weight change and strength of the cements in an acidic environment more than at pH 7.4. CONCLUSIONS: High apatite-forming activity and low degradation were the characteristics of a radiopaque dicalcium silicate cement.

In situ ATR-FTIR studies on MgCl2-diisobutyl phthalate interactions in thin film Ziegler-Natta catalysts.

To study the surface structure of MgCl(2) support and its interaction with other active components in Ziegler-Natta catalyst, such as electron donors, we prepared a thin film analogue for Ziegler-Natta ethylene polymerization catalyst support by spin-coating a solution of MgCl(2) in ethanol, optionally containing a diester internal donor (diisobutyl-ortho-phthalate, DIBP) on a flat Si crystal surface. The donor content of these films was quantified by applying attenuated total internal reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). Changes in the interaction of DIBP with MgCl(2) at various temperatures were monitored by in situ ATR-FTIR. Upon increasing the temperature, a shift in the (C═O) band toward lower wavenumbers was observed together with the depletion of (O-H) stretching band due to the desorption of residual ethanol. We assign this shift to gradual redistribution of adsorbed DIBP from adsorption sites on the MgCl(2) (104) surface toward the more acidic MgCl(2) (110) surface. The morphologies of MgCl(2) and MgCl(2)/DIBP films were studied by transmission electron microscopy (TEM) revealing a preferential orientation of ClMgCl layers (001) parallel to the lateral film dimensions. This orientation becomes more pronounced upon annealing. In the absence of donor, the MgCl(2) grow in to large crystals aligned in large domains upon annealing. Both crystal growth and alignment is impeded by the presence of donor.

Preparation of three-bore hollow fiber charged nanofiltration membrane for separation of organics and salts.

Three-bore hollow fiber charged nanofiltration (NF) membrane was prepared by interfacial polymerization (IP). The results showed that the flux and rejection of NF membrane prepared in this study increased with the increasing in the operating pressure. The water flux decreased and rejection for obvious dyes increased as the solute concentration increased. The separation factor for mixture of Xylenol orange/NaCl decreased when NaCl concentration in solution increased and could reach to as high as 18. In addition, three-bore hollow fiber charged nanofiltration membrane prepared in this study has excellent stability for strong acid (pH = 3), strong alkali (pH = 11) and high temperature solution (80 °C).

Actin protein inside DMPC GUVs and its mechanical response to AC electric fields.

Cells are dynamic systems with complex mechanical properties, regulated by the presence of different species of proteins capable to assemble (and disassemble) into filamentous forms as required by different cells functions. Giant unilamellar vesicles (GUVs) of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) are systems frequently used as a simplified model of cells because they offer the possibility of assaying separately different stimuli, which is no possible in living cells. Here we present a study of the effect of acting protein on mechanical properties of GUVs, when the protein is inside the vesicles in either monomeric G-actin or filamentous F-actin. For this, rabbit skeletal muscle G-actin is introduced inside GUVs by the electroformation method. Protein polymerization inside the GUVs is promoted by adding to the solution MgCl2 and the ion carrier A23187 to allow the transport of Mg+2 ions into the GUVs. To determine how the presence of actin changes the mechanical properties of GUVs, the vesicles are deformed by the application of an AC electric field in both cases with G-actin and with polymerized F-actin. The changes in shape of the vesicles are characterized by optical microscopy and from them the bending stiffness of the membrane are determined. It is found that G-actin has no appreciable effect on the bending stiffness of DMPC GUVs, but the polymerized actin makes the vesicles more rigid and therefore more resistant to deformations. This result is supported by evidence that actin filaments tend to accumulate near the membrane.

Behaviors in ethylene polymerization of MgCl2-SiO2/TiCl4/THF Ziegler-Natta catalysts with differently treated SiO2.

The present research focuses on investigation of the catalytic behaviors of MgCl2-SiO2/TiCl4/THF Ziegler-Natta (ZN) catalysts with fumed SiO2 variously treated with silane compounds. The non-treated silica (NTS) and other silicas treated with dimethylsilicone fluid (TSDMSF), dimethyldichlorosilane (TSDMDCS), and hexamethyl-disilazane (TSHMDS) were employed. It was found that the Cat-TSDMDCS and Cat-TSHMDS exhibited remarkably high activity, even with a similar bulk Ti content as the others. Thus, the more powerful technique of XPS analysis was used to determine the Ti content at the catalyst surface. It was evident that the surface concentrations of Ti could play important role on the catalyst activity. As the result, the increased activity is proportional to the surface concentration of Ti. It was mentioned that the change in surface concentration of Ti with different treated silica can be attributed to the effect of silane spacer group and steric hindrance. The distribution of Ti on the external surface can be also proven by means of EDX mapping, which matched the results obtained by XPS analysis. The treated silica also resulted in narrower molecular weight distribution (MWD) due to the more uniform active sites produced. There was no significant change in polymer morphology upon treatment of the silica.

A Salt Stimulus-Responsive Nanohydrogel for Controlled Fishing Low-Density Lipoprotein with Superior Adsorption Capacity.

A salt-responsive nanoplatform is constructed through a simple tactic by tethering zwitterionic nanohydrogels (NGs) on a carboxylated silica (SiO2-COOH) framework. Chondroitin sulfate (CS), with a specific recognition effect for low-density lipoprotein (LDL), is modified to NGs by amidation reaction. Water retention and swelling properties of NGs are greatly enhanced in a saline environment attributed to the anti-polyelectrolyte effect. It endows the SiO2-NGs-CS framework a sensitive salt-responsive property, and thus, more CS moieties are exposed. The controlled adsorption of LDL with an adsorption efficiency of 7.2 to 93% is achieved by adjusting the concentration of MgCl2 from 0 to 0.1 mol L-1. SiO2-NGs-CS exhibits excellent adsorption capacity for fishing LDL, acquiring the highest adsorption capacity of 898.1 mg g-1. Moreover, SiO2-NGs-CS shows superior selectivity to the other three proteins with similar isoelectric points (pIs) to LDL. The captured LDL is readily stripped by 0.2% (m/m) SDS with a recovery of 95.4%. The superior separation performance of SiO2-NGs-CS is demonstrated by the isolation and selective discrimination of LDL from the simulated serum of hypercholesterolemia patients, as illustrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis assays.

Pretreatment of lignocellulosic waste as a precursor for synthesis of high porous activated carbon and its application for Pb (II) and Cr (VI) adsorption from aqueous solutions.

Effects of Elm tree sawdust pretreatments using alkali and alkaline earth metals (NaCl, KCl, CaCl2, MgCl2 and Elm tree ash) and deashing solutions (water, HCl, HNO3 and aqua regia) before the carbonization process on the porosity of produced activated carbons and Pb (II) and Cr (VI) adsorption were studied. The activated carbons were characterized by pore size distribution, surface area, FTIR, and SEM-EDX analysies. Based on the results, HCl leaching pretreatment of the biomass increased the activated carbon adsorption capacity of Cr (VI) from 114 to 190 mg g-1. The treatment of biomass with alkali and alkali earth metal salts, especially MgCl2, remarkably increased the activated carbon adsorption capacity of Pb (II) from 233 to 1430 mg g-1. The results indicated that Pb (II) adsorption was attributed to both the mesoporous structure of activated carbon and the abundance of Mg on the activated carbon's surface. On the other hand, the micropores played a major role in Cr (VI) adsorption capacity. The development of the micro- or mesoporous structure of activated carbons through pretreatment of lignocellulosic precursor could be an approach for providing high performance activated carbons for Pb (II) and Cr (VI) removal from aqueous solutions.

The GTPase activity of Escherichia coli FtsZ determines the magnitude of the FtsZ polymer bundling by ZapA in vitro.

FtsZ polymerizes in a ring-like structure at mid cell to initiate cell division in Escherichia coli. The ring is stabilized by a number of proteins among which the widely conserved ZapA protein. Using antibodies against ZapA, we found surprisingly that the cellular concentration of ZapA is approximately equal to that of FtsZ. This raised the question of how the cell can prevent their interaction and thereby the premature stabilization of FtsZ protofilaments in nondividing cells. Therefore, we studied the FtsZ-ZapA interaction at the physiological pH of 7.5 instead of pH 6.5 (the optimal pH for FtsZ polymerization), under conditions that stimulate protofilament formation (5 mM MgCl(2)) and under conditions that stimulate and stabilize protofilaments (10 mM MgCl(2)). Using pelleting, light scattering, and GTPase assays, it was found that stabilization and bundling of FtsZ polymers by ZapA was inversely correlated to the GTPase activity of FtsZ. As GTP hydrolysis is the rate-limiting factor for depolymerization of FtsZ, we propose that ZapA will only enhance the cooperativity of polymer association during the transition from helical filament to mid cell ring and will not stabilize the short single protofilaments in the cytoplasm. All thus far published in vitro data on the interaction between FtsZ and ZapA have been obtained with His-ZapA. We found that in our case the presence of a His tag fused to ZapA prevented the protein to complement a DeltazapA strain in vivo and that it affected the interaction between FtsZ and ZapA in vitro.

Stabilization of three-way junctions of DNA under molecular crowding conditions.

We examined the effects of molecular crowding conditions on the structures and thermodynamics of three-way junctions (TWJs) of DNA. Structural analysis utilizing gel electrophoresis and circular dichroism spectroscopy showed that the designed DNAs folded into TWJ structures in the presence of Na(+) and Mg(2+) under both dilute and molecular crowding conditions with polyethylene glycol 200 (PEG 200). From the thermodynamic parameters evaluated by UV melting techniques in the absence and presence of 5 mM Mg(2+) under dilute and molecular crowding conditions, it was clear that Mg(2+) stabilized all TWJs under the dilute condition, although the extent of stabilization depended on the stacking partners of TWJs. For example, thermodynamic stability (-DeltaG(o) (37)) of A/B-stacked TWJs (A, B, and C are the three helices of TWJ, and among these helices, A and B are stacked together) increased from 3.7 to 5.6 kcal/mol by the addition of 5 mM Mg(2+), while that of A/C-stacked TWJs (A and C are stacked together) increased only from 3.0 to 3.7 kcal/mol. Molecular crowding with PEG 200 destabilized the whole TWJ consisting of a junction point and three helical duplex arms. Crowding agents such as PEG 200 can affect the stability of DNA by modulating its hydration. To explore the crowding effects on the junction point, we evaluated the number of water molecules associated with the whole TWJ as well as the individual arms, and we found that the number of water molecules taken up by the whole TWJ was significantly smaller than the sum of the individual arms. These results show the dehydration from the junction point of the TWJ structure. Therefore, molecular crowding should be favorable for the junction point of TWJ structure and unfavorable for the duplex structure. To prove this concept, we designed truncated TWJ structures that folded into a bimolecular duplex under the dilute condition. With increasing concentrations of PEG 200 from 0 to 30 wt %, the fraction of truncated TWJ structures gradually increased, and that of the bimolecular duplex structure decreased, even in the absence of Mg(2+). We concluded that a cell-mimicking condition, in which the activity of water decreases and hydration becomes less favorable, might facilitate the formation of junction structures in comparison with duplexes.

Equilibrium electrostatics of responsive polyelectrolyte monolayers.

The physical behavior of polyelectrolytes at solid-liquid interfaces presents challenges both in measurement and in interpretation. An informative, yet often overlooked, property that characterizes the equilibrium organization of these systems is their membrane or rest potential. Here a general classification scheme is presented of the relationship between the rest potential and structural response of polyelectrolyte films to salt concentration. A numerical lattice theory, adapted from the polymer community, is used to analyze the rest potential response of end-tethered polyelectrolyte layers in which electrostatics and short-range contact interactions conspire to bring about different structural states. As an experimental quantity the rest potential is a readily accessible, nonperturbing metric of the equilibrium structure of a polyelectrolyte layer. A first set of measurements is reported on monolayers of end-tethered, single-stranded DNA in monovalent (NaCl) and divalent (MgCl(2)) counterion environments. Intriguingly, in NaCl electrolyte at least two different mechanisms appear by which the DNA layers can structurally relax in response to changing salt conditions. In MgCl(2) the layers appear to collapse. The possible molecular mechanisms behind these behaviors are discussed. These studies provide insight into phenomena more generally underlying polyelectrolyte applications in the chemical, environmental, and biotechnological fields.

Co-catalysis of magnesium chloride and ferrous chloride for xylo-oligosaccharides and glucose production from sugarcane bagasse.

Inorganic salt treatment is a novel, high-yield, and environmentally friendly approach for the production of xylo-oligosaccharides from Sugarcane bagasse with degree of polymerization of 2-5. A xylo-oligosaccharides yield of 53.79% was obtained with 0.1 M MgCl2 treatment at 180 °C/10 min, and 41.89% with 0.1 M FeCl2 treatment at 140 °C/30 min. The xylo-oligosaccharides yield from the co-catalysis of 0.05 M FeCl2 + 0.05 M MgCl2 reached 54.68% (29.34% xylobiose and 20.94% xylotriose) at 140 °C/30 min. The co-catalysis not only effectively improved the xylobiose and xylotriose contents but also increased the total yield of xylo-oligosaccharides under mild reaction conditions. Additionally, the glucose yield observed from the solid residue after inorganic salt treatment was 71.62% by enzymatic hydrolysis. Mg2+ and Fe2+ are essential for good human health without separation from the system, therefore, the inorganic salt treatment can be potentially applied in the co-production of xylo-oligosaccharides and glucose.

One-Pot Assembly of Complex Giant Unilamellar Vesicle-Based Synthetic Cells.

Here, we introduce a one-pot method for the bottom-up assembly of complex single- and multicompartment synthetic cells. Cellular components are enclosed within giant unilamellar vesicles (GUVs), produced at the milliliter scale directly from small unilamellar vesicles (SUVs) or proteoliposomes with only basic laboratory equipment within minutes. Toward this end, we layer an aqueous solution, containing SUVs and all biocomponents, on top of an oil-surfactant mix. Manual shaking induces the spontaneous formation of surfactant-stabilized water-in-oil droplets with a spherical supported lipid bilayer at their periphery. Finally, to release GUV-based synthetic cells from the oil and the surfactant shell into the physiological environment, we add an aqueous buffer and a droplet-destabilizing agent. We prove that the obtained GUVs are unilamellar by reconstituting the pore-forming membrane protein α-hemolysin and assess the membrane quality with cryotransmission electron microscopy (cryoTEM), fluorescence recovery after photobleaching (FRAP), and zeta-potential measurements as well as confocal fluorescence imaging. We further demonstrate that our GUV formation method overcomes key challenges of standard techniques, offering high volumes, a flexible choice of lipid compositions and buffer conditions, straightforward coreconstitution of proteins, and a high encapsulation efficiency of biomolecules and even large cargo including cells. We thereby provide a simple, robust, and broadly applicable strategy to mass-produce complex multicomponent GUVs for high-throughput testing in synthetic biology and biomedicine, which can directly be implemented in laboratories around the world.

Sizing of single globular DNA molecules by using a circular acceleration technique with laser trapping.

We describe a method for in situ sizing individual huge DNA molecules by laser trapping. Single DNA molecules are reversibly transformed, without mechanical fragmentation of fragile huge-sized DNA, from their random coil state into their globular state induced by condensing agents poly(ethylene glycol) and Mg(2+). With the use of a globular DNA molecule folded by condensation, the critical velocity of the circularly accelerated single globular DNA molecule by laser trapping was found to be proportional to the size of the DNA. Yeast, Saccharomyces cerevisiae, chromosome III (285 kbp) was successfully sized (281 +/- 40 kbp) from a calibration curve scaled using lambda, T4, and yeast chromosome VI (48.5, 166, and 385 kbp, respectively). The use of critical velocity as a sizing parameter makes it possible to size single DNA molecules without prior conformational information, i.e., the radius of a single globular huge DNA molecule as a nanoparticle. A sized single globular DNA molecule could be trapped again for subsequent manipulation, such as transportation of it anywhere. We also investigated a possibility of reusing the globular DNA molecules condensed by PEG and Mg(2+) for PCR and found that PCR efficiency was not deteriorated in the presence of the condensation agents.

Effects of fluoride on the interactions between amelogenin and apatite crystals.

Fluorosed enamel is more porous and less mineralized, possibly related to altered amelogenin-modulated crystal growth. The purpose of this study was to examine the role of fluoride in interactions between amelogenin and apatite crystals. Recombinant human amelogenin (rh174) was bound to carbonated hydroxyapatite containing various amounts of fluoride, and analyzed by protein assay, SDS PAGE, and AFM. Interactions between rh174 and fluoride were assayed by isothermal titration calorimetry (ITC). The initial binding rate of rh174, as well as total amount of rh174 bound to fluoride-containing carbonated hydroxyapatite, was greater than that in the control carbonated hydroxyapatite. Fluoride in solution at physiologic (5.3 micromolar, or 0.1 ppm) concentrations showed no significant effect on binding, but higher fluoride levels significantly decreased protein binding. ITC showed no interactions between fluoride and rh174. These results suggest that fluoride incorporation into the crystal lattice alters the crystal surface to enhance amelogenin binding, with no direct interactions between fluoride and amelogenin.

Influence of magnesium chloride on the dose-response of polyacrylamide-type gel dosimeters.

We investigated the effect of magnesium chloride (MgCl2) on the nuclear magnetic resonance dose-response of polyacrylamide-type (PAGAT, NIPAM, and VIPET) gel dosimeters containing acrylamide, N-isopropylacrylamide, and N-vinylpyrrolidone as a monomer, respectively. The dose-transverse relaxation rates (1/T2 = R2) obtained from magnetic resonance imaging data revealed that a substantial increase in the dose-R2 response occurred as the concentration of MgCl2 in the gel dosimeters increased. The sensitivity of the PAGAT gel with 1.0 M MgCl2 was found to be approximately one order higher than that of the same gel without MgCl2. In addition, the water equivalences of the gels with MgCl2 were evaluated over a wide range of photon energies. The results indicated that MgCl2 acts as a powerful sensitizer to radiation-induced free-radical polymerization in polyacrylamide-type gel dosimeters, but does not interfere with the desirable properties of basic polyacrylamide-type gel dosimeters (i.e., the dose rate and dose integration).

Poly(N-vinyl-pyrrolidone)-block-poly(D,L-lactide) as polymeric emulsifier for the preparation of biodegradable nanoparticles.

Poly(D,L-lactide) (PDLLA) amphiphilic block copolymers were employed as emulsifiers in the preparation of PDLLA nanoparticles by an oil/water emulsion solvent evaporation technique. The surface-active properties of poly(N-vinyl-pyrrolidone)-block-poly(D,L-lactide) (PVP-b-PDLLA) toward the biphasic system were compared to those of polyethylene glycol(PEG)-b-PDLLA of similar composition. PVP-b-PDLLA was found to be a suitable emulsifier for dichloromethane/water emulsions, yielding narrowly distributed nanoparticles (<250 nm) surrounded by a hydrophilic PVP corona. PEG-b-PDLLA, however, was only effective in producing appropriately sized nanoparticles when dichloromethane was replaced with ethyl acetate. Furthermore, the lyoprotectant properties of PVP allowed the freeze-dried nanoparticles to recover their initial size following reconstitution, while PEG-coated nanoparticles could not be redispersed following lyophilization. Two poorly water-soluble drugs, that is, paclitaxel and etoposide, were efficiently loaded into PVP-decorated PDLLA nanoparticles. The entrapment efficiency of etoposide was significantly enhanced by adding MgCl2 to the aqueous phase. It was found that the nanoparticles released the drugs progressively over several days in vitro. The obtained experimental results were corroborated with the theoretical compatibility between a given drug, polymer, and solvent, predicted by total solubility parameters.