Yanjing Chen

Controlled Release from Bilayer-Decorated Magnetoliposomes via Electromagnetic Heating

Nanoscale assemblies that can be activated and controlled through external stimuli represent a next stage in multifunctional therapeutics. We report the formation, characterization, and release properties of bilayer-decorated magnetoliposomes (dMLs) that were prepared by embedding small hydrophobic SPIO nanoparticles at different lipid molecule to nanoparticle ratios within dipalmitoylphosphatidylcholine (DPPC) bilayers. The dML structure was examined by cryogenic transmission electron microscopy and differential scanning calorimetry, and release was examined by carboxyfluorescein leakage. Nanoparticle heating using alternating current electromagnetic fields (EMFs) operating at radio frequencies provided selective release of the encapsulated molecule at low nanoparticle concentrations and under physiologically acceptable EMF conditions. Without radio frequency heating, spontaneous leakage from the dMLs decreased with increasing nanoparticle loading, consistent with greater bilayer stability and a decrease in the effective dML surface area due to aggregation. With radio frequency heating, the initial rate and extent of leakage increased significantly as a function of nanoparticle loading and electromagnetic field strength. The mechanism of release is attributed to a combination of bilayer permeabilization and partial dML rupture.

Development of novel lithium borate additives for designed surface modification of high voltage LiNi0.5Mn1.5O4 cathodes

A novel series of lithium alkyl trimethyl borates and lithium aryl trimethyl borates have been prepared and investigated as cathode film forming additives. The borates are prepared via the reaction of lithium alkoxides or lithium phenoxides with trimethyl borate. Incorporation of 0.5–2.0% (wt) of the lithium borates to a baseline electrolyte (1.0 M LiPF6 in 3 : 7 (EC/EMC)) results in improved capacity retention and efficiency of high voltage graphite/LiNi0.5Mn1.5O4 cells especially upon cycling at elevated temperature (55 °C). The improved performance results from the sacrificial oxidation of the lithium borate on the cathode surface to generate a cathode passivation film. The lithium borates can be readily structurally modified to act as a functional group delivery agent to modify the cathode surface. Ex situ surface analysis of the electrodes after cycling confirms that the lithium borates modify the cathode surface and generate a borate rich surface film which inhibits electrolyte oxidation and Mn dissolution.

Multicomponent folate-targeted magnetoliposomes: design, characterization, and cellular uptake

UNLABELLED Folate-targeted cationic magnetoliposomes (FTMLs) have been prepared with coencapsulated doxorubicin (DOX) and anionic superparamagnetic iron oxide (SPIO) nanoparticles (NPs) with 5 nm γ-Fe(2)O(3) cores and 16 nm hydrodynamic diameters. NP encapsulation (89%) was confirmed by cryogenic transmission electron microscopy (TEM), and the presence of the oppositely charged NPs did not cause liposome aggregation. The FTMLs had an average diameter of 174 ± 53 nm and existed as unilamellar and cup-shaped liposomes, which was attributed to dissimilar lipid packing parameters and the presence of PEG-lipids. A 3-fold increase in DOX release was achieved over 2 hours when the encapsulated SPIO NPs were heated by an alternating current electromagnetic field operating at radio frequencies (RF). Results with human cervical cancer cells (HeLa), which have been shown to exhibit high folate receptor (FR) expression, confirmed FTML surface binding and cellular uptake. In contrast, no uptake was observed for lower FR-expressing human breast carcinoma cells (ZR-75-1). FROM THE CLINICAL EDITOR This study discusses the design and cellular uptake of multifunctional folate-targeted cationic magnetoliposomes enabling doxorubicin delivery and SPIO labeling.

Structural and Thermal Analysis of Lipid Vesicles Encapsulating Hydrophobic Gold Nanoparticles

The structure and stability of hybrid lipid vesicles containing bilayer-encapsulated hydrophobic nanoparticles is dependent upon lipid phase behavior. By embedding stearylamine-stabilized gold nanoparticles in dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylglycerol vesicles, we show that encapsulation at lipid to nanoparticle ratios from 10,000:1 to 5000:1 leads to bilayer thickening and hydrophobic mismatch, favoring nanoparticle inclusion in gel phase vesicles. High loadings lead to large increases in the gel to fluid melting temperature upon heating and significant hysteresis on cooling, which cannot be attributed solely to excess free ligand. This behavior is due to a cooperative effect of excess free SA ligand and nanoparticle embedment. Nanoparticle clustering was observed during lipid melting and could be reversed upon lipid freezing owing to lateral capillary forces within the bilayer. The impact of nanoparticle embedment on vesicle structure and properties at such low concentrations is reminiscent of hydrophobic proteins, suggesting that the underlying lipid biophysics between proteins and nanoparticle are similar and may provide a predictive design tool for therapeutic applications.

Lipid-assisted formation and dispersion of aqueous and bilayer-embedded nano-C60.

Lipid assemblies provide a biocompatible approach for preparing aqueous nanoparticles. In this work, dipalmitoylphosphatidylcholine (DPPC) was used to assist in the formation and dispersion of C(60) and nano-C(60) aggregates using a modified reverse phase evaporation (REV) method. This method led to the rapid formation of aqueous nano-C(60) at DPPC/C(60) molar ratios from 500:1 to 100:1 (12-38 nm; verified by cryogenic transmission electron microscopy), which were present in the bulk phase and encapsulated within vesicles. In addition to forming nanoparticles, C(60) was trapped within the vesicle bilayer and led to a reduction in the lipid melting temperature. Solvent extraction was used to isolate nano-C(60) from the lipids and bilayer-embedded C(60). Our results suggest that bilayer-embedded C(60) was present as molecular C(60) and as small amorphous nano-C(60) (2.3 +/- 0.4 nm), which clustered in the aqueous phase after the lipids were extracted. In addition to developing a new technique for nano-C(60) formation, our results suggest that the lipid bilayer may be used as a hydrophobic region for dispersing and assembling small nano-C(60).

High Capacity, Stable Silicon/Carbon Anodes for Lithium-Ion Batteries Prepared Using Emulsion-Templated Directed Assembly

Silicon (Si) is a promising candidate for lithium ion battery anodes because of its high theoretical capacity. However, the large volume changes during lithiation/delithiation cycles result in pulverization of Si, leading to rapid fading of capacity. Here, we report a simple fabrication technique that is designed to overcome many of the limitations that deter more widespread adoption of Si based anodes. We confine Si nanoparticles in the oil phase of an oil-in-water emulsion stabilized by carbon black (CB). These CB nanoparticles are both oil- and water-wettable. The hydrophilic/hydrophobic balance for the CB nanoparticles also causes them to form a network in the continuous aqueous phase. Upon drying this emulsion on a current collector, the CB particles located at the surfaces of the emulsion droplets form mesoporous cages that loosely encapsulate the Si particles that were in the oil. The CB particles that were in the aqueous phase form a conducting network connected to the CB cages. The space within the cages allows for Si particle expansion without transmitting stresses to the surrounding carbon network. Half-cell experiments using this Si/CB anode architecture show a specific capacity of ∼1300 mAh/g Si + C and a Coulombic efficiency of 97.4% after 50 cycles. Emulsion-templating is a simple, inexpensive processing strategy that directs Si and conducts CB particles to desired spatial locations for superior performance of anodes in lithium ion batteries.

Effect of lamellarity and size on calorimetric phase transitions in single component phosphatidylcholine vesicles.

Nano-differential scanning calorimetry (nano-DSC) is a powerful tool in the investigation of unilamellar (small unilamellar, SUVs, or large unilamellar, LUVs) vesicles, as well as lipids on supported bilayers, since it measures the main gel-to-liquid phase transition temperature (Tm), enthalpies and entropies. In order to assign these transitions in single component systems, where Tm often occurred as a doublet, nano-DSC, dynamic light scattering and cryo-transmission electron microscopy (cryo-TEM) data were compared. The two Tms were not attributable to decoupled phase transitions between the two leaflets of the bilayer, i.e. nano-DSC measurements were not able to distinguish between the outer and inner leaflets of the vesicle bilayers. Instead, the two Tms were attributed to mixtures of oligolamellar and unilamellar vesicles, as confirmed by cryo-TEM images. Tm for the oligolamellar vesicles was assigned to the peak closest to that of the parent multilamellar vesicle (MLV) peak. The other transition was higher than that of the parent MLVs for 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and increased in temperature as the vesicle size decreased, while it was lower in temperature than that of the parent MLVs for 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and decreased as the vesicle size decreased. These subtle shifts arose due to small differences in the values of ΔH and ΔS, since Tm is determined by their ratio (ΔH/ΔS). It was not possible to completely eliminate oligolamellar structures for MLVs extruded with the 200 nm pore size filter, even after 120 passes, while these structures were eliminated for MLVs extruded through the 50 nm pore size filter.

Formation of lipid sheaths around nanoparticle-supported lipid bilayers.

High-surface-area nanoparticles often cluster, with unknown effects on their cellular uptake and environmental impact. In the presence of vesicles or cell membranes, lipid adsorption can occur on the nanoparticles, resulting in the formation of supported lipid bilayers (SLBs), which tend to resist cellular uptake. When the amount of lipid available is in excess compared with that required to form a single-SLB, large aggregates of SLBs enclosed by a close-fitting lipid bilayer sheath are shown to form. The proposed mechanism for this process is one where small unilamellar vesicles (SUVs) adsorb to aggregates of SLBs just above the gel-to-liquid phase transition temperature, T(m) , of the lipids (as observed by dynamic light scattering), and then fuse with each other (rather than to the underlying SLBs) upon cooling below T(m) . The sacks of SLB nanoparticles that are formed are encapsulated by the contiguous close-fitting lipid sheath, and precipitate below T(m) , due to reduced hydration repulsion and the absence of undulation/protrusion forces for the lipids attached to the solid support. The single-SLBs can be released above T(m) , where these forces are restored by the free lipid vesicles. This mechanism may be useful for encapsulation/release of drugs/DNA, and has implications for the toxic effects of nanoparticles, which may be mitigated by lipid sequestration.

All-Aqueous Directed Assembly Strategy for Forming High-Capacity, Stable Silicon/Carbon Anodes for Lithium-Ion Batteries

Silicon (Si) particles have emerged as a promising active material for next-generation lithium-ion battery anodes. However, the large volume changes during lithiation/delithiation cycles result in fracture and pulverization of Si, leading to rapid fading of performance. Here, we report a simple, all-aqueous, directed assembly-based strategy to fabricate Si-based anodes that show capacity and capacity retention that are comparable or better than other more complex methods for forming anodes. We use a cationic surfactant, cetyltrimethylammonium bromide (CTAB), to stabilize Si nanoparticles (SiNPs) in water. This suspension is added to an aqueous suspension of para-amino benzoic acid-terminated carbon black (CB), pH 7. Charge interactions cause the well-dispersed SiNP to bind to the CB, allowing most of the SiNP to be available for lithiation and charge transfer. The CB forms a conducting network when the suspension pH is lowered. The dried SiNP/CTAB/CB anode exhibits a capacity of 1580 mAh g(-1) and efficiency of 97.3% after 50 cycles at a rate of 0.1C, and stable performance at cycling rates up to 5C. The directed spatial organization of the SiNP and CB using straightforward colloidal principles allows good contact between the well-dispersed active material and the electrically conducting network. The pore space in the CB network accommodates volume changes in the SiNPs. When CTAB is not used, the SiNPs form aggregates in the suspension, and do not contact the CB effectively. Therefore, the electrochemical performance of the SiNP/CB anode is inferior to that of the SiNP/CTAB/CB anode. This aqueous-based, room temperature, directed assembly technique is a new, but simple, low-cost scalable method to fabricate stable Si-based anodes for lithium-ion batteries with performance characteristics that match those made by other more sophisticated techniques.