Showing papers by "Weiwei Gao published in 2013"

Surface Functionalization of Gold Nanoparticles with Red Blood Cell Membranes

Abstract: Gold nanoparticles are enclosed in cellular membranes derived from natural red blood cells (RBCs) by a top-down approach. The gold nanoparticles exhibit a complete membrane surface layer and biological characteristics of the source cells. The combination of inorganic gold nanoparticles with biological membranes is a compelling way to develop biomimetic gold nanostructures for future applications, such as those requiring evasion of the immune system.

Interfacial interactions between natural RBC membranes and synthetic polymeric nanoparticles

Abstract: The unique structural features and stealth properties of a recently developed red blood cell membrane-cloaked nanoparticle (RBC-NP) platform raise curiosity over the interfacial interactions between natural cellular membranes and polymeric nanoparticle substrates. Herein, several interfacial aspects of the RBC-NPs are examined, including completeness of membrane coverage, membrane sidedness upon coating, and the effects of polymeric particles' surface charge and surface curvature on the membrane cloaking process. The study shows that RBC membranes completely cover negatively charged polymeric nanoparticles in a right-side-out manner and enhance the particles' colloidal stability. The membrane cloaking process is applicable to particle substrates with a diameter ranging from 65 to 340 nm. Additionally, the study reveals that both surface glycans on RBC membranes and the substrate properties play a significant role in driving and directing the membrane-particle assembly. These findings further the understanding of the dynamics between cellular membranes and nanoscale substrates and provide valuable information toward future development and characterization of cellular membrane-cloaked nanodevices.

‘Marker-of-self’ functionalization of nanoscale particles through a top-down cellular membrane coating approach

Abstract: We investigate the ‘marker-of-self’ functionalization of nanoparticles through coating of natural RBC membranes. The membrane translocation approach is shown to be highly efficient and bestows nanoparticles with correctly oriented and functional immunomodulatory proteins such as CD47 at equivalent density to natural RBCs.

Lipid-insertion enables targeting functionalization of erythrocyte membrane-cloaked nanoparticles

Abstract: RBC membrane-cloaked polymeric nanoparticles represent an emerging nanocarrier platform with extended circulation in vivo. A lipid-insertion method is employed to functionalize these nanoparticles without the need for direct chemical conjugation. Insertion of both folate and the nucleolin-targeting aptamer AS1411 shows receptor-specific targeting against model cancer cell lines.

Liposome-like Nanostructures for Drug Delivery

Abstract: Liposomes are a class of well-established drug carriers that have found numerous therapeutic applications. The success of liposomes, together with recent advancements in nanotechnology, has motivated the development of various novel liposome-like nanostructures with improved drug delivery performance. These nanostructures can be categorized into five major varieties, namely: (1) polymer-stabilized liposomes, (2) nanoparticle-stabilized liposomes, (3) core–shell lipid–polymer hybrid nanoparticles, (4) natural membrane-derived vesicles, and (5) natural membrane coated nanoparticles. They have received significant attention and have become popular drug delivery platforms. Herein, we discuss the unique strengths of these liposome-like platforms in drug delivery, with a particular emphasis on how liposome-inspired novel designs have led to improved therapeutic efficacy, and review recent progress made by each platform in advancing healthcare.

Nanoparticle-stabilized liposomes for pH-responsive gastric drug delivery

Abstract: We report a novel pH-responsive gold nanoparticle-stabilized liposome system for gastric antimicrobial delivery. By adsorbing small chitosan-modified gold nanoparticles (diameter ~10 nm) onto the outer surface of negatively charged phospholipid liposomes (diameter ~75 nm), we show that at gastric pH the liposomes have excellent stability with limited fusion ability and negligible cargo releases. However, when the stabilized liposomes are present in an environment with neutral pH, the gold stabilizers detach from the liposomes, resulting in free liposomes that can actively fuse with bacterial membranes. Using Helicobacter pylori as a model bacterium and doxycycline as a model antibiotic, we demonstrate such pH-responsive fusion activity and drug release profile of the nanoparticle-stabilized liposomes. Particularly, at neutral pH the gold nanoparticles detach, and thus the doxycycline-loaded liposomes rapidly fuse with bacteria and cause superior bactericidal efficacy as compared to the free doxycycline counterpart. Our results suggest that the reported liposome system holds a substantial potential for gastric drug delivery; it remains inactive (stable) in the stomach lumen but actively interacts with bacteria once it reaches the mucus layer of the stomach where the bacteria may reside.

In Vivo Treatment of Propionibacterium acnes Infection with Liposomal Lauric Acids

Abstract: Propionibacterium acnes (P. acnes) is a Gram-positive bacterium strongly associated with acne infection. While many antimicrobial agents have been used in clinic to treat acne infection by targeting P. acnes, these existing anti-acne agents usually produce considerable side effects. Herein, the development and evaluation of liposomal lauric acids (LipoLA) is reported as a new, effective and safe therapeutic agent for the treatment of acne infection. By incorporating lauric acids into the lipid bilayer of liposomes, it is observed that the resulting LipoLA readily fuse with bacterial membranes, causing effective killing of P. acnes by disrupting bacterial membrane structures. Using a mouse ear model, we demonstrated that the bactericidal property of LipoLA against P. acne is well preserved at physiological conditions. Topically applying LipoLA in a gel form onto the infectious sites leads to eradication of P. acnes bacteria in vivo. Further skin toxicity studies show that LipoLA does not induce acute toxicity to normal mouse skin, while benzoyl peroxide and salicylic acid, the two most popular over-the-counter acne medications, generate moderate to severe skin irritation within 24 h. These results suggest that LipoLA hold a high therapeutic potential for the treatment of acne infection and other P. acnes related diseases.

Spontaneous formation of heterogeneous patches on polymer-lipid core-shell particle surfaces during self-assembly.

Abstract: Nanoparticle (NP) surfaces have been widely investigated and engineered due to their importance in the synthesis of particles for targeted drug delivery, vaccination, medical imaging, as well as personal care products, and electronics.[1] For instance in drug delivery, the ability to functionalize the surface of NPs with ligands for differential delivery of drugs has demonstrated increased target cell uptake compared to equivalent NPs lacking the ligands.[2] Similarly, modification of the surface of inorganic NP such as quantum dots, iron oxide, and gold NPs, has been explored to render them biocompatible and non-toxic for applications in therapeutics and diagnostics.[3] Common methods used to characterize particle physicochemical properties include nuclear magnetic resonance (NMR), surface plasmon resonance (SPR), X-ray diffraction (XRD), and dynamic light scattering (DLS), among others.[4] However, while these techniques tend to measure the properties of a population of particles, they tend to overlook the surface characteristics of single particles such as ligand distribution and charge density distribution over the particle surface, which could greatly impact their expected interaction with cells, proteins or other particles.

Origin of Different Growth Modes for Epitaxial Manganite Films

Abstract: The microstructures of the Bi0.4Ca0.6MnO3 (BCMO) and La0.67Ca0.33MnO3 (LCMO) epitaxial films are investigated by transmission electron microscopy in detail. BCMO epitaxial films (similar to 10 and similar to 40nm) exhibit an island growth mode whereas the LCMO films (similar to 6 and similar to 30nm) follow a layer by layer growth mode. Combined with the critical thickness models for the expected onset of the misfit dislocations in epitaxial films, an atomic collapse model is introduced to explain their mechanism of formation in manganite films. At the beginning of deposition, the strain caused by the lattice mismatch between the epitaxial film and substrate can be accommodated by elastic deformation. With the increase of film thickness, the strain becomes larger and larger. When the film thickness reaches the critical thickness, the strain can only be relaxed by the formation of misfit dislocations. Meanwhile, the atomic configuration of the epitaxial film will reorganize and some atoms begin to collapse, thus an island morphology will be formed. Once the collapse morphology is formed, maintenance of this wave-like morphology depends on atomic diffusion length of the deposited atoms. If the diffusion length of the deposited atoms is long, the island morphology will not be maintained. If the diffusion length of the deposited atoms is short, the island morphology will keep until the epitaxial film is thick enough. The results could shed light on the growth modes for other perovskite epitaxial films.

Photoelectronic behaviors of bilayer ultrathin films manganite-based heterojunctions

Abstract: We presented a systematic study on the photoelectronic properties of the La0.67Ba0.33MnO3 (20 nm)/LaMnO3(t)/SrTiO3:0.05 wt. % Nb (LBMO/LMO(t)/STON) junctions with 0 ≤ t ≤ 30 nm. The short-circuit photocurrent (Iph) is found to show a complex dependence on the LMO buffer layer. It undergoes first a sharp drop as the layer thickness of LMO increases from 0 to 3 nm and then, after a rigid turn, a slow decrease for further increase in layer thickness. These results indicate that the coupling between LBMO and STON can be effectively depressed by a LMO layer of 3 nm. The photocurrent is further found to be temperature dependent, increasing monotonically upon cooling, and the maximal growth, occurring in the junction of t = 3 nm, can be as high as 226% when cooled from 320 K to 40 K. Meanwhile, the Iph-t dependences at different temperatures are similar, which is an indication of temperature independence for the diffusion length of the photocarriers. Analysis of the capacitance-voltage relations indicates that t...