Porous Nanoparticle Supported Lipid Bilayers (Protocells) as Delivery Vehicles

Abstract

Mixing liposomes with hydrophilic particles will induce fusion of the liposome onto the particle surface. Such supported bilayers have been extensively studied as a model for the cell membrane, while its application in drug delivery has not been pursued. In this communication, we report the use of phospholipids to achieve synergistic loading and encapsulating of a fluorescent dye (calcein) in mesoporous silica nanoparticles, and its delivery into mammalian cells. We found that cationic lipid DOTAP provides the highest calcein loading with the concentration inside silica ∼110× higher than that in the solution under experimental conditions. Compared to some other nanoparticle systems, protocells provide a simple construct for loading, sealing, delivering and releasing, and should serve as a useful system in nanomedicine.One of the major challenges in nanomedicine is to engineer nanostructures and materials that can efficiently encapsulate drugs at high concentration, cross the cell membrane, and controllably release the cargo at the target site over a prescribed period of time. 1 Recently, inorganic nanoparticles, including gold, silica, and carbon nanotubes have emerged as a new generation of drug/therapy delivery vehicles in nanomedicine. 2,3 Mesoporous silica nanoparticles are particularly attractive in this regard, because of their biocompatibility and their precisely defined nanoporosity. 4-7 With uniform, tunable pore diameters, ranging from ∼2-5-nm and surfaces areas of 700-1500 m 2 /g, drugs and other components can be loaded by adsorption or capillary filling, and the release profiles adjusted by the combination of pore size and pore surface chemistry. 8 Very recently, elegant gating methods, employing coumarin, 9 azobenzene, 10,11 rotaxane, 12 polymers, 13,14 or small nanoparticles, 15,16 have been established to seal the cargo within the particle and allow its triggered release according to an optical or electrochemical stimulus. Here we describe a synergistic system where liposome fusion on a mesoporous silica particle core simultaneously loads and seals the cargo, creating a 'protocell' construct useful for delivery across the cell membrane (Fig. 1B). We observe that fusion of a positively charged liposome on a negatively charged mesoporous silica core serves to load the core with a negatively charged dye (excluded from the mesopores without lipid) to concentrations that can exceed 100x those in solution. Sealed within the protocell, this membrane impermeable dye can be transported across the cell membrane and slowly released within the cell. Compared to other nanoparticle delivery systems, the protocell is simple and takes advantage of the low toxicity and immunogenicity of liposomes along with their ability to be PEGylated or conjugated to extend circulation time and effect targeting. Compared to liposomes, however, the protocell is more stable and takes advantage of the mesoporous core to control both loading and release. As noted in many other relevant papers the mesoporous E-mail: cjbrink...

Interfacing Zwitterionic Liposomes with Inorganic Nanomaterials: Surface Forces, Membrane Integrity, and Applications

“…While most experiments were performed on planar silica surfaces, silica NPs were also studied. [17][18][19][20][21][22] These studies set a solid basis for exploring the interaction between PC liposomes with other types of inorganic NPs.…”

A Stable Lipid/TiO2 Interface with Headgroup-Inversed Phosphocholine and a Comparison with SiO2

“…[1][2][3][4][5] Phosphocholine (PC) lipids deposited on silica (SiO2) is the most commonly used system since PC liposomes readily fuse with silica under physiological conditions. [6][7][8][9][10][11] In addition, PC liposomes are zwitterionic and highly biocompatible. A thin water layer (~1 nm) separates the PC headgroup from the silica surface to achieve a mobile bilayer.…”

Mesoporous Silica Nanoparticles: A Review

“…By chemical modification of the surface of MSNs, [119] coating with proteins and polymers [112] and lipid bilayer coating particle aggregation can be decreased [117,118,121]. By using these methods steric hindrance and electrostatic repulsion is achieved, as a result stable saline dispersion of MSNs is formed [106].…”