Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI
نویسندگان
چکیده
Ligand-conjugated microparticles of iron oxide (MPIO) have the potential to provide high sensitivity contrast for molecular magnetic resonance imaging (MRI). However, the accumulation and persistence of non-biodegradable micron-sized particles in liver and spleen precludes their clinical use and limits the translational potential of MPIO-based contrast agents. Here we show that ligand-targeted MPIO derived from multiple iron oxide nanoparticles may be coupled covalently through peptide linkers that are designed to be cleaved by intracellular macrophage proteases. The synthesized particles possess potential characteristics for targeted MRI contrast agents, including high relaxivity, unappreciable sedimentation, clearance from circulation and no overt toxicity. Importantly, we demonstrate that these particles are rapidly degraded both in vitro and in vivo, and that the targeted probes can be used for detection of inflammation in vivo using MRI. This approach provides a platform for molecular MRI contrast agents that is potentially more suitable for translation to humans.
منابع مشابه
Covalent assembly of nanoparticles as a peptidase - degradable platform for 1 molecular MRI
9 Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, 10 Department of Oncology, University of Oxford, Oxford, OX3 7DQ,UK 11 Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, 12 OX1 3TA,UK. 13 Department of Cardiovascular Medicine and Oxford Acute Vascular Imaging Centre, 14 University of Oxford, John Radcliffe Hospital, Oxf...
متن کاملEngineering Nano-aggregates: β-Cyclodextrin Facilitates the Thiol-Gold Nanoparticle Self-Assembly
The structure and morphology of nonmaterial formed by colloidal synthesis represent a subject of interest as it is a factor deciding the physicochemical properties and biological applications of nanostructures. Among various nanoparticles, gold can develop fractal assembled patterns. Herein, we report a nano-aggregate of a thiol-on-gold self-assembled structure and the influence of β-cyclodextr...
متن کاملA New Theranostic System Based on Gd2O3 NPs coated Polycyclodextrin Functionalized Glucose for Molecular Magnetic Resonance Imaging (MMRI).
Introduction: Recent advances in nanoscience and biomedicine have attracted tremendous attention over the past decade to design and construct multifunctional nanoparticles that combine targeting, therapeutic, and diagnostic functions with a single platform to overcome the problems of conventional techniques for diagnosis and therapy with minimal toxicity. Materials ...
متن کاملSynthesis and characterization of supramolecule self-assembly polyamidoamine (PAMAM) G1-G1 NH2, CO2H end group Megamer
Supramolecule self assembly polyamidoamine (PAMAM) dendrimer refers to the chemical systems made up of a discrete number of assembled molecular subunits or components. These strategies involve the covalent assembly of hierarchical components reactive monomers, branch cells or dendrons around atomic or molecular cores according to divergent/convergent dendritic branching principles, systematic f...
متن کاملProstate stem cell antigen-targeted nanoparticles with dual functional properties: in vivo imaging and cancer chemotherapy
BACKGROUND We designed dual-functional nanoparticles for in vivo application using a modified electrostatic and covalent layer-by-layer assembly strategy to address the challenge of assessment and treatment of hormone-refractory prostate cancer. METHODS Core-shell nanoparticles were formulated by integrating three distinct functional components, ie, a core constituted by poly(D,L-lactic-co-gl...
متن کامل