Sarah Angelos

Bio: Sarah Angelos is an academic researcher from University of California, Los Angeles. The author has contributed to research in topics: Mesoporous silica & Molecular machine. The author has an hindex of 12, co-authored 14 publications receiving 2464 citations. Previous affiliations of Sarah Angelos include University of California.

Enzyme-Responsive Snap-Top Covered Silica Nanocontainers

Abstract: Mesoporous silica nanoparticles, capable of storing a payload of small molecules and releasing it following specific catalytic activation by an esterase, have been designed and fabricated. The storage and release of the payload is controlled by the presence of [2]rotaxanes, which consist of tri(ethylene glycol) chains threaded by α-cyclodextrin tori, located on the surfaces of the nanoparticles and terminated by a large stoppering group. These modified silica nanoparticles are capable of encapsulating guest molecules when the [2]rotaxanes are present. The bulky stoppers, which serve to hold the tori in place, are stable under physiological conditions but are cleaved by the catalytic action of an enzyme, causing dethreading of the tori and release of the guest molecules from the pores of the nanoparticles. These snap-top covered silica nanocontainers (SCSNs) are prepared by a modular synthetic method, in which the stoppering unit, incorporated in the final step of the synthesis, may be changed at will to target the response of the system to any of a number of hydrolytic enzymes. Here, the design, synthesis, and operation of model SCSNs that open in the presence of porcine liver esterase (PLE) are reported. The empty pores of the silica nanoparticles were loaded with luminescent dye molecules (rhodamine B), and stoppering units that incorporate adamantyl ester moieties were then attached in the presence of α-cyclodextrin using the copper-catalyzed azide−alkyne cycloaddition (CuAAC), closing the SCSNs. The release of rhodamine-B from the pores of the SCSN, following PLE-mediated hydrolysis of the stoppers, was monitored using fluorescence spectroscopy.

pH‐Responsive Supramolecular Nanovalves Based on Cucurbit[6]uril Pseudorotaxanes

Abstract: The ability to control the release of molecules from mesoporous silica nanoparticles promises to have far-reaching consequences for drug-delivery applications. Both molecular and supramolecular nanovalves, which regulate the release of guest molecules from nanopores of mesostructured silica nanoparticles, and operate under a range of stimuli including pH, competitive binding, light, and redox control, have been designed and their successful operation demonstrated in organic solvents. These systems are based upon the switching of components that have been tethered to the nanoparticle surfaces, such that access to the entrances of the nanopores can be opened and gated on demand. Since most of the traditional nanovalve designs have been based on [2]pseudorotaxanes and bistable [2]rotaxanes that rely upon donor–acceptor and hydrogen-bonding interactions between the ring and stalk components, they are limited largely to use in organic solvents. However, to realize the potential of nanovalves in therapeutic applications, it is imperative that they not only employ biocompatible components but that they also operate under physiological conditions. For nanovalves to be viable in biological environments, a recognition and binding motif which operates in aqueous media has to be identified, and then tried and tested. Herein, we describe a pH-responsive nanovalve that relies on the ion–dipole interaction between cucurbit[6]uril (CB[6]) and bisammonium stalks, and operates in water. CB[6], a pumpkin-shaped polymacrocycle with D6h symmetry consisting of six glycouril units strapped together by pairs of bridging methylene groups between nitrogen atoms, has received considerable attention because of its highly distinctive range of physical and chemical properties. Of particular interest in the field of supramolecular chemistry is the ability of CB[6] to form inclusion complexes with a variety of polymethylene derivatives, especially diaminoalkanes: the stabilities of these 1:1 complexes are highly pHdependent. The pH-dependent complexation/decomplexation behavior of CB[6] with diaminoalkanes has enabled the preparation of dynamic supramolecular entities which can be controlled by pH. Another important characteristic of CB[6] is its ability to catalyze 1,3-dipolar cycloadditions, such that the reaction between an azide-substituted ammonium ion and an alkyne-containing ammonium ion yields a disubstituted 1,2,3-triazole derivative encircled by a CB[6] ring. In view of these particular properties of CB[6], we set about to employ it as a catalyst for the formation of monolayers of [2]pseudorotaxanes on the surfaces of mesoporous silica nanoparticles so as to generate ultimately pHresponsive, biocompatible nanovalves capable of executing different missions. Mesoporous silica has proven to be an excellent support for the formation of dynamic nanosystems, including nanovalves, because it is chemically stable and optically transparent. In this current study, [2]pseudorotaxanes consisting of bisammonium stalks and CB[6] rings were constructed (Figure 1a,b) on the surface of mesoporous silica nanoparticles, and the pH-dependent binding of CB[6] with the bisammonium stalks is exploited to control the release of guest molecules from the pores of the silica nanoparticles. At neutral and acidic pH values, the CB[6] rings encircle the bisammonium stalks tightly, thereby blocking the nanopores efficiently when employing tethers of suitable lengths. Deprotonation of the stalks upon addition of base results in spontaneous dethreading (Figure 1b,c) of the CB[6] rings and unblocking of the silica nanopores. The silica supports employed were approximately 400nm-diameter spherical particles which contain ordered 2D hexagonal arrays of tubular pores (pore diameters of ca. 2 nm with a lattice spacing of ca. 4 nm) prepared by using a basecatalyzed sol–gel method. The nanopores were templated by cetyltrimethylammonium bromide (CTAB) surfactants, and tetraethylorthosilicate (TEOS) was used as the silica precursor. Empty nanopores were obtained by removal of the templating agents by solvent extraction. The ordered structure and particle morphology were confirmed (Figure 2) by X-ray diffraction (XRD) and scanning electron microscopy. This system was designed (Scheme 1a) such that the nanovalve components could be assembled in a stepwise, divergent manner from the nanoparticle surface outwards. Following solvent extraction, the nanoparticles were heated under reflux in an aminopropyltriethoxysilane (APTES) solution, which afforded the amino-modified nanoparticles 1. These nanoparticles were recovered by vacuum filtration [*] S. Angelos, Dr. Y.-W. Yang, K. Patel, Prof. J. F. Stoddart, Prof. J. I. Zink California NanoSystems Institute and Department of Chemistry and Biochemistry University of California, Los Angeles 405 Hilgard Avenue, Los Angeles, CA 90095-1569 (USA) Fax: (+1)310-206-1843 E-mail: stoddart@chem.ucla.edu zink@chem.ucla.edu Homepage: http://stoddart.chem.ucla.edu http://www.chem.ucla.edu/dept/Faculty/jzink/ [] These authors have contributed equally and both should be considered first author.

pH clock-operated mechanized nanoparticles.

Abstract: Mechanized nanoparticles (MNPs) consisting of supramolecular machines attached to the surface of mesoporous silica nanoparticles are designed to release encapsulated guest molecules controllably under pH activation. The molecular machines are comprised of cucurbit[6]uril (CB[6]) rings that encircle tethered trisammonium stalks and can be tuned to respond under specific pH conditions through chemical modification of the stalks. Luminescence spectroscopy demonstrates that the MNPs are able to contain guest molecules within nanopores at neutral pH levels and then release them once the pH is lowered or raised.

Dual-controlled nanoparticles exhibiting AND logic.

Abstract: Dual-controlled nanoparticles (DCNPs) are synthesized by attaching two different types of molecular machines, light-responsive nanoimpellers and pH-responsive nanovalves, to different regions of mesoporous silica nanoparticles. Nanoimpellers are based on azobenzene derivatives that are tethered to the nanopore interiors, while nanovalves are based on [2]pseudorotaxanes that are tethered to the nanoparticle surfaces. The different molecular machines operate through separate mechanisms to control the release of guest molecules that are loaded into the nanopores. When used in conjunction with one another, a sophisticated controllable release system behaving as an AND logic gate is obtained.

Photo-Driven Expulsion of Molecules from Mesostructured Silica Nanoparticles

Abstract: Azobenzene derivatives act as both impellers and gatekeepers when they are tethered in and on mesoporous silica nanoparticles. Continuous excitation at 457 nm, a wavelength where both the cis and trans conformers absorb, produces constant isomerization reactions and results in continual dynamic wagging of the untethered terminus. The 2 nm diameter pores are loaded with luminescent probe molecules, azobenzene motion is stimulated by light, and the photoinduced expulsion of the probe from the particles that is caused by the motion is monitored by luminescence spectroscopy. The light-responsive nature of these materials enables them to be externally controlled such that the expulsion of dye molecules from the mesopores can be started and stopped at will. These results open the possibilities of trapping useful molecules such as drugs and releasing them on demand.

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。

Mesoporous Silica Nanoparticles: Synthesis, Biocompatibility and Drug Delivery

Abstract: In the past decade, mesoporous silica nanoparticles (MSNs) have attracted more and more attention for their potential biomedical applications. With their tailored mesoporous structure and high surface area, MSNs as drug delivery systems (DDSs) show significant advantages over traditional drug nanocarriers. In this review, we overview the recent progress in the synthesis of MSNs for drug delivery applications. First, we provide an overview of synthesis strategies for fabricating ordered MSNs and hollow/rattle-type MSNs. Then, the in vitro and in vivo biocompatibility and biotranslocation of MSNs are discussed in relation to their chemophysical properties including particle size, surface properties, shape, and structure. The review also highlights the significant achievements in drug delivery using mesoporous silica nanoparticles and their multifunctional counterparts as drug carriers. In particular, the biological barriers for nano-based targeted cancer therapy and MSN-based targeting strategies are discussed. We conclude with our personal perspectives on the directions in which future work in this field might be focused.

Mesoporous silica nanoparticles in biomedical applications

Abstract: This tutorial review provides an outlook on nanomaterials that are currently being used for theranostic purposes, with a special focus on mesoporous silica nanoparticle (MSNP) based materials. MSNPs with large surface area and pore volume can serve as efficient carriers for various therapeutic agents. The functionalization of MSNPs with molecular, supramolecular or polymer moieties, provides the material with great versatility while performing drug delivery tasks, which makes the delivery process highly controllable. This emerging area at the interface of chemistry and the life sciences offers a broad palette of opportunities for researchers with interests ranging from sol–gel science, the fabrication of nanomaterials, supramolecular chemistry, controllable drug delivery and targeted theranostics in biology and medicine.

Artificial Molecular Machines

Abstract: The widespread use of molecular machines in biology has long suggested that great rewards could come from bridging the gap between synthetic molecular systems and the machines of the macroscopic world. In the last two decades, it has proved possible to design synthetic molecular systems with architectures where triggered large amplitude positional changes of submolecular components occur. Perhaps the best way to appreciate the technological potential of controlled molecular-level motion is to recognize that nanomotors and molecular-level machines lie at the heart of every significant biological process. Over billions of years of evolution, nature has not repeatedly chosen this solution for performing complex tasks without good reason. When mankind learns how to build artificial structures that can control and exploit molecular level motion and interface their effects directly with other molecular-level substructures and the outside world, it will potentially impact on every aspect of functional molecule and materials design. An improved understanding of physics and biology will surely follow. The first steps on the long path to the invention of artificial molecular machines were arguably taken in 1827 when the Scottish botanist Robert Brown observed the haphazard motion of tiny particles under his microscope.1,2 The explanation for Brownian motion, that it is caused by bombardment of the particles by molecules as a consequence of the kinetic theory of matter, was later provided by Einstein, followed by experimental verification by Perrin.3,4 The random thermal motion of molecules and its implications for the laws of thermodynamics in turn inspired Gedankenexperiments (“thought experiments”) that explored the interplay (and apparent paradoxes) of Brownian motion and the Second Law of Thermodynamics. Richard Feynman’s famous 1959 lecture “There’s plenty of room at the bottom” outlined some of the promise that manmade molecular machines might hold.5,6 However, Feynman’s talk came at a time before chemists had the necessary synthetic and analytical tools to make molecular machines. While interest among synthetic chemists began to grow in the 1970s and 1980s, progress accelerated in the 1990s, particularly with the invention of methods to make mechanically interlocked molecular systems (catenanes and rotaxanes) and control and switch the relative positions of their components.7−24 Here, we review triggered large-amplitude motions in molecular structures and the changes in properties these can produce. We concentrate on conformational and configurational changes in wholly covalently bonded molecules and on catenanes and rotaxanes in which switching is brought about by various stimuli (light, electrochemistry, pH, heat, solvent polarity, cation or anion binding, allosteric effects, temperature, reversible covalent bond formation, etc.). Finally, we discuss the latest generations of sophisticated synthetic molecular machine systems in which the controlled motion of subcomponents is used to perform complex tasks, paving the way to applications and the realization of a new era of “molecular nanotechnology”. 1.1. The Language Used To Describe Molecular Machines Terminology needs to be properly and appropriately defined and these meanings used consistently to effectively convey scientific concepts. Nowhere is the need for accurate scientific language more apparent than in the field of molecular machines. Much of the terminology used to describe molecular-level machines has its origins in observations made by biologists and physicists, and their findings and descriptions have often been misinterpreted and misunderstood by chemists. In 2007 we formalized definitions of some common terms used in the field (e.g., “machine”, “switch”, “motor”, “ratchet”, etc.) so that chemists could use them in a manner consistent with the meanings understood by biologists and physicists who study molecular-level machines.14 The word “machine” implies a mechanical movement that accomplishes a useful task. This Review concentrates on systems where a stimulus triggers the controlled, relatively large amplitude (or directional) motion of one molecular or submolecular component relative to another that can potentially result in a net task being performed. Molecular machines can be further categorized into various classes such as “motors” and “switches” whose behavior differs significantly.14 For example, in a rotaxane-based “switch”, the change in position of a macrocycle on the thread of the rotaxane influences the system only as a function of state. Returning the components of a molecular switch to their original position undoes any work done, and so a switch cannot be used repetitively and progressively to do work. A “motor”, on the other hand, influences a system as a function of trajectory, meaning that when the components of a molecular motor return to their original positions, for example, after a 360° directional rotation, any work that has been done is not undone unless the motor is subsequently rotated by 360° in the reverse direction. This difference in behavior is significant; no “switch-based” molecular machine can be used to progressively perform work in the way that biological motors can, such as those from the kinesin, myosin, and dynein superfamilies, unless the switch is part of a larger ratchet mechanism.14