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COLL Abstracts COLL 1 Cytosolic internalization of luminescent quantum dots Hedi M. Mattoussi1, [email protected], Anshika Kapur1, Goutam Palui1, Wentao Wang1, Scott Medina2, Joel Schneider2. (1) Chem Biochem, Florida State University, Tallahassee, Florida, United States (2) Center for Cancer Research, National Cancer Institute, , Frederick, Maryland, United States The remarkable progress made over the past two decades to grow inorganic nanomaterials, combined with careful surface functionalization strategies offer an opportunity to develop novel platforms for use in molecular imaging and as diagnostic tools. A successful integration into biological systems requires devising strategies to promote their intracellular uptake while circumventing endocytosis. We report on the use of an amphiphilic anti-microbial peptide as means of promoting the cytosolic uptake of luminescent QDs. The peptide is synthesized with a terminal cysteine to allow conjugation onto QDs that have been coated with multifunctional metal-coordinating ligands. Using fluorescence imaging and flow cytometry we find that incubating cells with the QD-peptide leads to delivery into the cytoplasm without affecting the cellular morphology or viability. We observed a homogeneous distribution of QD staining throughout the cytoplasm and without co-localization with labelled endosomes. Additional experiments where endocytosis has been eliminated (such as pre-treatment with specific inhibitors) have shown minimal effects on the intracellular QD uptake. COLL 2 Influence of PEGyalation on the interaction of colloids with cells Wolfgang Parak1,2, [email protected]. (1) Universitaet Marburg, Marburg, Germany (2) CIC Biomagune, San Sebastian, Spain Several homologous nanoparticle libraries were synthesized in which inorganic nanoparticles (Au, FePt) were coated with polyethylene glycol (PEG). In the first series the molecular weight of the PEG was systematically increased. In the second series the diameter of Au cores as well as the thickness of the shell of polyethylene glycol was varied, keeping the resulting diameter constant. Basic physicochemical parameters of this two-dimensional nanoparticle library, such as size, z-potential, hydrophilicity, elasticity, catalytic activity, as well as protein adsorption were determined. Uptake of the nanoparticles by cells lines, and their effect on basic structural and functional cell parameters was determined. COLL 3 Engineered nanomaterials for protein and nucleic acid delivery Vincent M. Rotello, [email protected]. Univ of Massachusetts, Amherst, Massachusetts, United States Therapeutic delivery of proteins and nucleic acids is a difficult goal. Of the many challenges in the delivery process, perhaps the most demanding is providing these biologics with access to the cytosol. Most delivery strategies employ endosomal uptake, requiring endosomal escape for the payload biologics to be effective. In our research, we have developed an alternative strategy that uses nanoparticle-stabilized nanocapsules (NPSCs) to deliver proteins and nucleic acids (siRNA and DNA) directly to the cytosol. These NPSCs use a membrane fusion process to bypass the endosomal pathway, providing highly effective payload delivery. The direct access to the cytosol makes NPSCs effective tools for therapeutic delivery, particularly in conjunction with intracellular targeting. Applications in vitro, in vivo, and mechanistic studies of these vehicles will be discussed. COLL 4 Supramolecular bioactive nanostructures for cell signaling Samuel I. Stupp, [email protected]. Northwestern University, Evanston, Illinois, United States Signaling pathways and other cell functions mediated by the extracellular matrix involve filamentous nanostructures that interact with receptors. This lecture will describe supramolecular nanostructures that mimic these nanostructures, created with biomolecular structural units including modified peptides, glycans, and nucleic acids. The systems to be described have the capacity to signal cells and promote biological adhesion, proliferation, and differentiation of stem cells. The lecture will demonstrate the functionality of these structures both in vitro and in vivo in the context of regenerative medicine and also systemic targeted therapies. The lecture will also discuss the design of dynamic bioactivity in these nanostructures that can be switched “on” or “off” using soluble chemical signals. Other features to be discussed include their capacity to bind multiple proteins for complex signaling, and also their ability to control cell signaling by changing the properties of cell membranes. COLL 5 Optimizing passivation of interfaces with zwitterions Joseph B. Schlenoff, [email protected]. Florida State Univ, Tallahassee, Florida, United States Zwitterionic functionality at an interface is known to be highly effective at reducing interactions with (bio)macromolecules. Such “nonfouling” surfaces are found in nature and are increasingly being used to moderate interactions of nanoparticles with the in vivo environment. In particular, a nonfouling background decorated with ligands of high specificity is frequently a target of nanoparticle synthesis. Several morphologies for passivating nanoparticles with zwitterions are available, ranging from a monolayer of functional units to a thick brush of zwitterionic polymer. To prepare these zwitterion coatings, the chemistry for surface attachment, ligand density and zwitterion chemistry must be optimized. This talk will address various ways of anchoring zwitterions to surfaces and the performance against aggregation of the resulting planar and nanoparticle materials. Fundamental understanding of the mechanism for zwitterion nonfouling properties will be highlighted. At least one example of counterintuitive/surprising zwitterion behavior will presented. COLL 6 Nanoparticles interactions with viruses Francesco Stellacci, [email protected]. Institute of Materials, EPFL, Lausanne, Switzerland Viruses perform many roles when interacting with humans. They are responsible for millions of deaths worldwide due to a plethora of transmissible diseases that they create. At the same time they are key components in vaccines and are used as transfection agents in modern medicine. These amazing self-assembled biological objects are nanoscale in size and hence potentially could interact with nanoparticles in a variety of -mostly unexplored- ways. In this talk, I will show how most functions of viruses can be affected by the interaction with small gold nanoparticles, leading to innovative ideas in medicine. COLL 7 Smart and bright: Functional luminescent nanoparticles for bioimaging and therapy Gang Han, [email protected]. Biochemistry and Molecular Pharmacology , University of Massachusetts-Medical school, Worcester, Massachusetts, United States Functional luminescent nanoparticles are promising materials for in vitro and in vivo optical imaging and therapy due to their unique optical and chemical properties. In this talk, I will present two new types of biocompatible luminescence nanoparticles. The first type of materials is upconversion nanoparticles (UCNPs). They absorb low energy near-infrared (NIR) light and emit high-energy shorter wavelength photons. Their special features allow them to overcome various problems associated with conventional imaging probe at both single molecule and ensemble levels. I will present new developments regarding engineering UCNPs towards deep tissue imaging, photodynamic therapy, optogenetic applications in neuroscience and immunotherapy. The second type of nanoparticles is persistent luminescence nanoparticles (PLNPs). They are bioluminescence-like and possess unprecedented in vivo deep tissue energy rechargeability, outstanding signal-to-noise-ratio with no need for an excitation resource (light) during imaging, and they can be directly detected with existing imaging systems. These nanoparticles continue to emit light for minutes or hours and, in some cases, days, after turning off the excitation source. These long-lasting, light-emitting nanocrystals can provide noninvasive imaging technology for evaluating structural and functional biological processes in living animals and patients. COLL 8 Ionic functionalization of hydrophobic colloidal nanoparticles to form ionic nanoparticles with enzyme-like properties Yuan Liu2, [email protected], Weihong Tan1. (1) Univ of Florida, Gainesville, Florida, United States (2) Chemistry, University of Florida, Gainesville, Florida, United States Inorganic colloidal nanoparticles (NPs) stabilized by a layer of hydrophobic surfactant on their surfaces have poor solubility in the aqueous phase, thus limiting their application as biosensors under physiological conditions. Here we report a simple model to ionize various types of hydrophobic colloidal NPs, including FePt, cubic Fe3O4, Pd, CdSe, and NaYF4 (Yb 30%, Er 2%, Nd 1%) NPs, to multicharged (positive and negative) NPs via ligand exchange. Surfaces of neutral hydrophobic NPs were converted to multicharged ions, thus making them soluble in water. Furthermore, peroxidase-like activity was observed for ionic FePt, Fe3O4, Pd, and CdSe NPs, of which FePt and CdSe catalyzed the oxidation of the colorless substrate 3,3′,5,5′- tetramethylbenzidine (TMB) to the blue-colored product in the absence of H2O2, while Pd and Fe3O4 catalyzed the oxidization of TMB in the presence of H2O2. With the benefit of the ionic functionalization protocols described herein, colloidal
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