Surface Chemistry Architecture of Silica Nanoparticles Determine the Efficiency of in Vivo Fluorescence Lymph Node Mapping

Abstract

Near-infrared (NIR) imaging of the lymphatic system offers a sensitive, versatile, and accurate lymph node mapping to locate the first, potentially metastatic, draining nodes in the operating room. Many luminescent nanoprobes have received great attention in this field, and the design of nontoxic and bright nanosystems is of crucial importance. Fluorescent NIR-emitting dye doped silica nanoparticles represent valuable platforms to fulfill these scopes, providing sufficient brightness, resistance to photobleaching, and hydrophilic nontoxic materials. Here, we synthesized these highly stable core-shell nanoparticles with a programmable surface charge positioning and determined the effect of these physicochemical properties on their in vivo behavior. In addition, we characterized their fluorescence kinetic profile in the right axillary lymph node (RALN) mapping. We found that nanoparticles with negative charges hidden by a PEG shell are more appropriate than those with external negative charges in the mapping of lymph nodes. We also demonstrated the efficient excretion of these nanostructures by the hepatobiliary route and their nontoxicity in mice up to 3 months postinjection. These results indicate the potential future development of these fluorescent nanosystems for LN mapping.

Fluorescent Silica Nanoparticles with Multivalent Inhibitory Effects towards Carbonic Anhydrases

“…[5,6] Due to their size, ease of synthesis, andt heir potentiala pplications, silica-based nanoparticles received great attention for their biomedical applications both for the site-specific delivery of drugs or for imaging purposes. [7][8][9] Moreoveri tc onstitutes ag ood platform for developing multivalent interactions,w hich is ap romising option for the specific treatment of diseases.Multivalent enzymei nhibitors that combine multiple copies of an inhibitor conjugated to as ingle scaffold may lead to an overall increase of the bindinga ffinity,a vidity,a nd/or specificity.[10] These changes that are associated with the multivalentp resentation of inhibitors dependo nt he nature of the biological target andm ay arise from differentm echanisms: 1) as tatistical rebinding effect,2 )a chelate effect, 3) as ubsite binding effect, or 4) ac lustering effect.[11] Though the multivalency approachh as been extensively studied in the context of lectins that contain multiple binding sites, [12] its application in the field of enzyme inhibition has received less attention until recently.F or instance, the multivalency strategy has been successfully appliedi nt he case of glycosidase inhibitors. [13][14] In the case of carbonic anhydrase, only studies on bivalent inhibitors were recently reported.I ndeed, Whiteside'sr esearch group describedi n2 012 the binding of monovalent and bivalent benzene sulfonamide ligandst oasynthetic dimer of carbonic anhydrase.…”

“…[a] Mean from three different assays, errorsi nt he range of AE 10 %o ft he reported values (data not shown). rp:r elativep otency = K I (10)/K I (9). rp/n:relativepotency/numberofs ulfonamideunits.…”

Applications of nanoparticles in cancer medicine and beyond: optical and multimodalin vivoimaging, tissue targeting and drug delivery

“…In particular, among the inorganic nanoformulations, silica-based nanomaterials have been investigated mainly because of: i) the fine size-control; and ii) a chemistry suitable for surface modification [4][5][6]. Based on these properties, several investigators, including our group, have considered SiNPs for applications as sensors [7], drug delivery systems [8] and/or bioimaging probes [9][10][11][12]. Metallic (iron oxide, gold, silver) NPs have been used for a huge number of applications in various areas of medical treatment and are emerging as tool for imaging, diagnosis, and for the delivery of therapeutic agents to tumor cells [13][14][15].…”

Silica nanoparticles induce reversible damage of spermatogenic cells via RIPK1 signal pathways in C57 mice

“…14,19,30 Oxidative stress might be related to the chemical and surface characteristics of the NPs, 31 which may be connected with the surface chemical architecture, hydroxyl groups, and compartmentalized cellular modification. [32][33][34] Owing to the special characteristics, NPs could interact with the mitochondria after NPs exposure. 35 Furthermore, NPs can disrupt the electron transport chain, decrease the mitochondrial membrane potential, hinder the Ca 2+ uptake, and increase the permeability of the mitochondria, which then leads to mitochondrial damage and finally induces oxidative stress.…”