Monty Liong

Bio: Monty Liong is an academic researcher from University of California, Los Angeles. The author has contributed to research in topics: Mesoporous silica & Drug delivery. The author has an hindex of 19, co-authored 20 publications receiving 9197 citations.

Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties.

Abstract: Nanomaterials (NM) exhibit novel physicochemical properties that determine their interaction with biological substrates and processes. Three metal oxide nanoparticles that are currently being produced in high tonnage, TiO2, ZnO, and CeO2, were synthesized by flame spray pyrolysis process and compared in a mechanistic study to elucidate the physicochemical characteristics that determine cellular uptake, subcellular localization, and toxic effects based on a test paradigm that was originally developed for oxidative stress and cytotoxicity in RAW 264.7 and BEAS-2B cell lines. ZnO induced toxicity in both cells, leading to the generation of reactive oxygen species (ROS), oxidant injury, excitation of inflammation, and cell death. Using ICP-MS and fluorescent-labeled ZnO, it is found that ZnO dissolution could happen in culture medium and endosomes. Nondissolved ZnO nanoparticles enter caveolae in BEAS-2B but enter lysosomes in RAW 264.7 cells in which smaller particle remnants dissolve. In contrast, fluoresce...

Multifunctional Inorganic Nanoparticles for Imaging, Targeting, and Drug Delivery

Abstract: Drug delivery, magnetic resonance and fluorescence imaging, magnetic manipulation, and cell targeting are simultaneously possible using a multifunctional mesoporous silica nanoparticle. Superparamagnetic iron oxide nanocrystals were encapsulated inside mesostructured silica spheres that were labeled with fluorescent dye molecules and coated with hydrophilic groups to prevent aggregation. Water-insoluble anticancer drugs were delivered into human cancer cells; surface conjugation with cancer-specific targeting agents increased the uptake into cancer cells relative to that in non-cancerous fibroblasts. The highly versatile multifunctional nanoparticles could potentially be used for simultaneous imaging and therapeutic applications.

Biocompatibility, Biodistribution, and Drug-Delivery Efficiency of Mesoporous Silica Nanoparticles for Cancer Therapy in Animals

Abstract: Mesoporous silica nanoparticles (MSNs) are a promising material for drug delivery. In this Full Paper, MSNs are first shown to be well tolerated, as demonstrated by serological, hematological, and histopathological examinations of blood samples and mouse tissues after MSN injection. Biodistribution studies using human cancer xenografts are carried out with in vivo imaging and fluorescent microscopy imaging, as well as with inductively coupled plasma mass spectroscopy. The results show that MSNs preferentially accumulate in tumors. Finally, the drug-delivery capability of MSNs is demonstrated by following tumor growth in mice treated with camptothecin-loaded MSNs. These results indicate that MSNs are biocompatible, preferentially accumulate in tumors, and effectively deliver drugs to the tumors and suppress tumor growth.

Mesoporous Silica Nanoparticles as a Delivery System for Hydrophobic Anticancer Drugs

Abstract: A critical obstacle and challenge for cancer therapy concerns the limited availability of effective biocompatible delivery systems for most hydrophobic therapeutic anticancer drugs. It is particularly important to improve the aqueous solubility of drugs, as low drug solubility in aqueous media hampers the ability of drugs to be administered through the intravenous route. Since many important anticancer agents have poor water solubility, the development of novel delivery systems for these molecules without the use of organic solvents has received significant attention. Nanoparticles offer great potential and a promising approach to deliver therapeutic agents into targeted organs or cells and they have been actively developed for application in cancer therapy. We have incorporated a representative hydrophobic anticancer drug, camptothecin (CPT), into the pores of fluorescent mesoporous silica nanoparticles (FMSNs) and delivered the drug into a variety of human cancer cells to induce cell death, a procedure suggesting that the mesoporous silica nanoparticles might be used as a vehicle to overcome the insolubility problem of many anticancer drugs. CPT and its derivatives are considered to be among the most promising anticancer drugs of the 21st century. Although studies have demonstrated their effectiveness against carcinomas of the stomach, colon, neck, and bladder, as well as breast and small-cell lung cancers, and leukemia, in vitro, clinical application of CPT in humans has not been achieved to date because the poor water solubility of the drug requires changes to the physicochemical characteristics. The need to formulate water-soluble salts of CPT (that is, alkaline solutions for intravenous injections) led to chemical modifications of the molecule with loss of antiACHTUNGTRENNUNGtumor activity and significant alterations in the toxicological profile of the drug. Although derivatives such as irinotecan have produced good clinical results, irinotecan was shown to have far lower cytotoxicity to cancer cells than CPT (10%), and CPT remains the most potent compound. Among a variety of drug-delivery systems, mesoporous silica materials have several attractive features for use in the delivery of water-insoluble drugs. These particles have large surface areas and porous interiors that can be used as reservoirs for storing hydrophobic drugs. The pore size and environment can be tailored to selectively store different molecules of interest, while the size and shape of the particles can be tuned to maximize cellular uptake. Unlike polymer-based nanoparticles, these robust inorganic materials can tolerate many organic solvents. Silica-based materials have been successfully used as drug-delivery vectors, gene transfection reagents, cell markers, and carriers of molecules. Here, we describe the preparation of fluorescent mesoporous silica nanoparticles that are highly stable in aqueous solution and their use for the delivery of the hydrophobic anticancer drug CPT. The FMSNs were prepared by using a base-catalyzed sol–gel process at high temperature with a modification of published procedures. 25,26] In a typical synthesis, fluorescein isothiocyanate (FITC) was first treated with 3-aminopropyltriethoxysilane (APTS) in ethanol. The mixture was then added, along with tetraethylorthosilicate, to cetyltriACHTUNGTRENNUNGmethylammonium bromide solution at 80 8C. The surfactants were removed from the pores by refluxing the nanoparticles in acidic methanol, the success of which was confirmed by Fourier transform infrared spectroscopy (FTIR; see Supporting Information). Electron microscopy and Xray diffraction (XRD) analysis showed that the particle shape and hexagonal arrays of the pores in the FMSNs remained intact after the surfactant-removal process (Figure 1). The nanoparticles were roughly spherical in shape and smaller than 130 nm in diameter. An average pore diameter of around 2 nm was observed by using transmission electron microscopy (TEM) and an interplanar spacing of dACHTUNGTRENNUNG(100) 4 nm was calculated from the XRD pattern. It is necessary for efficient cellular uptake of the particles that the FMSNs remain dispersed and do not aggregate in the buffer solution. The observed aggregation is caused by interparticle hydrogen-bonding interactions between the amine groups (from the unreacted APTS) and the silanols (Scheme 1A). By modifying only the surfaces of the FMSNs with trihydroxysilylpropyl methylphosphonate (THMP) after particle formation, we reduced the aggregation and increased the stability of the particles in aqueous solution (Scheme 1B, see Supporting Information). [*] Dr. J. Lu, Prof. F. Tamanoi Department of Microbiology, Immunology, and Molecular Genetics California NanoSystems Institute, JCCC University of California, Los Angeles 609 Charles E. Young Drive East, Los Angeles, CA 90095 (USA) Fax: (+1)310-206-5231 E-mail: fuyut@microbio.ucla.edu

Polyethyleneimine Coating Enhances the Cellular Uptake of Mesoporous Silica Nanoparticles and Allows Safe Delivery of siRNA and DNA Constructs

Abstract: Surface-functionalized mesoporous silica nanoparticles (MSNP) can be used as an efficient and safe carrier for bioactive molecules. In order to make the MSNP a more efficient delivery system, we modified the surface of the particles by a functional group that enhances cellular uptake and allows nucleic acid delivery in addition to traditional drug delivery. Noncovalent attachment of polyethyleneimine (PEI) polymers to the surface not only increases MSNP cellular uptake but also generates a cationic surface to which DNA and siRNA constructs could be attached. While efficient for intracellular delivery of these nucleic acids, the 25 kD PEI polymer unfortunately changes the safety profile of the MSNP that is otherwise very safe. By experimenting with several different polymer molecular weights, it was possible to retain high cellular uptake and transfection efficiency while reducing or even eliminating cationic MSNP cytotoxicity. The particles coated with the 10 kD PEI polymer were particularly efficient for transducing HEPA-1 cells with a siRNA construct that was capable of knocking down GFP expression. Similarly, transfection of a GFP plasmid induced effective expression of the fluorescent protein in >70% cells in the population. These outcomes were quantitatively assessed by confocal microscopy and flow cytometry. We also demonstrated that the enhanced cellular uptake of the nontoxic cationic MSNP enhances the delivery of the hydrophobic anticancer drug, paclitaxel, to pancreatic cancer cells. In summary, we demonstrate that, by a careful selection of PEI size, it is possible to construct cationic MSNP that are capable of nucleotide and enhanced drug delivery with minimal or no cytotoxicity. This novel use of a cationic MSNP extends its therapeutic use potential.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Understanding biophysicochemical interactions at the nano–bio interface

Abstract: Rapid growth in nanotechnology is increasing the likelihood of engineered nanomaterials coming into contact with humans and the environment. Nanoparticles interacting with proteins, membranes, cells, DNA and organelles establish a series of nanoparticle/biological interfaces that depend on colloidal forces as well as dynamic biophysicochemical interactions. These interactions lead to the formation of protein coronas, particle wrapping, intracellular uptake and biocatalytic processes that could have biocompatible or bioadverse outcomes. For their part, the biomolecules may induce phase transformations, free energy releases, restructuring and dissolution at the nanomaterial surface. Probing these various interfaces allows the development of predictive relationships between structure and activity that are determined by nanomaterial properties such as size, shape, surface chemistry, roughness and surface coatings. This knowledge is important from the perspective of safe use of nanomaterials.

Metal-organic frameworks in biomedicine.

Abstract: Metal Organic Frameworks in Biomedicine Patricia Horcajada,* Ruxandra Gref, Tarek Baati, Phoebe K. Allan, Guillaume Maurin, Patrick Couvreur, G erard F erey, Russell E. Morris, and Christian Serre* Institut Lavoisier, UMR CNRS 8180, Universit e de Versailles St-Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles Cedex, France Facult e de Pharmacie, UMR CNRS 8612, Universit e Paris-Sud, 92296 Châtenay-Malabry Cedex, France Institut Charles Gerhardt Montpellier, UMR CNRS 5253, Universit e Montpellier 2, 34095 Montpellier cedex 05, France EaStChem School of Chemistry, University of St. Andrews Purdie Building, St Andrews, KY16 9ST U.K.

Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes

Abstract: Over the past few decades, researchers have established artificial enzymes as highly stable and low-cost alternatives to natural enzymes in a wide range of applications. A variety of materials including cyclodextrins, metal complexes, porphyrins, polymers, dendrimers and biomolecules have been extensively explored to mimic the structures and functions of naturally occurring enzymes. Recently, some nanomaterials have been found to exhibit unexpected enzyme-like activities, and great advances have been made in this area due to the tremendous progress in nano-research and the unique characteristics of nanomaterials. To highlight the progress in the field of nanomaterial-based artificial enzymes (nanozymes), this review discusses various nanomaterials that have been explored to mimic different kinds of enzymes. We cover their kinetics, mechanisms and applications in numerous fields, from biosensing and immunoassays, to stem cell growth and pollutant removal. We also summarize several approaches to tune the activities of nanozymes. Finally, we make comparisons between nanozymes and other catalytic materials (other artificial enzymes, natural enzymes, organic catalysts and nanomaterial-based catalysts) and address the current challenges and future directions (302 references).