Design of a dendrimer with a matrix metalloproteinase-responsive fluorescence probe and a tumor-homing peptide for metastatic tumor cell imaging in the lymph node.

Fluorescence imaging is a noninvasive technique for cancer diagnosis. Dendrimers are regularly branched macromolecules with highly controllable size and structure that are a potent multifunctional nanoparticle. Anionic-terminal polyamidoamine (PAMAM) dendrimers were previously found to be accumulated in the lymph node, which is one of the main routes of tumor metastasis. In this study, we designed and synthesized a dendrimeric imaging probe for lymph node-resident tumor cell imaging. A matrix metalloproteinase-2 (MMP-2)-responsive fluorescence peptide probe and a tumor-homing peptide were conjugated to the carboxy-terminal dendrimer. The dendrimeric imaging probe treatment showed fluorescence signals inside some tumor cells (e.g., human fibrosarcoma HT-1080 and breast cancer 4T1 cells), depending on the MMP activity, but not in macrophage-like RAW264 cells.

Carboxyl-, sulfonyl-, and phosphate-terminal dendrimers as a nanoplatform with lymph node targeting.

The development of drug delivery vehicles to cancer and/or immune cells in lymph nodes is important for cancer diagnosis, therapy, and immunotherapy. We previously reported that anionic carboxyl-terminal dendrimers were accumulated in lymph nodes. In this study, three anionic dendrimers with carboxyl-, sulfonyl-, and phosphate-terminal groups were prepared to examine the lymph node targeting and the association with immune cells in the lymph nodes. These anionic dendrimers were accumulated in the lymph node by intradermal injection. Although the carboxyl- and sulfonyl-terminal dendrimers were diffused from the injection site, the phosphate-terminal dendrimers were mostly retained. The phosphate-terminal dendrimer was recognized by the macrophages, dendritic cells, and B cells in the lymph node, whereas the carboxyl- and sulfonyl-terminal dendrimers were not. Our results show that these anionic dendrimers were accumulated in the lymph node where the association with immune cells could be controlled by the terminal structure of the dendrimer. The phosphate-terminal dendrimer can be used as a nanoplatform for the delivery of some bioactive molecules to some immune cells, including B cells, in the lymph node.

Extraction Mechanism of Lanthanide Ions into Silica-based Microparticles Studied by Single Microparticle Manipulation and Microspectroscopy.

Single porous silica microparticles coated with a styrene-divinylbenzene polymer (SDB) impregnated with octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO) were injected into an aqueous 3 mol/L nitric acid solution containing trivalent lanthanide (Ln(III)), as a high-level liquid waste model. We used the microcapillary manipulation-injection technique; and the extraction rate of Ln(III), as an Ln(III)-CMPO complex, into the single microparticles was measured by luminescence microspectroscopy. The extraction rate significantly depended on the Ln(III), CMPO, or NO3- concentration, and was analyzed in terms of diffusion in the pores of the microparticles and the complex formation of Ln(III). The results indicated that the rate-determining step in Ln(III) extraction was diffusion in the pore solution of the microparticles.

Kinetic Analysis of the Solvent Extraction of Cadmium(II) Complexes Using a Cadmium-deposited Recessed Microelectrode and Confocal Fluorescence Microscope.

Using a Cd-deposited microelectrode, an electrochemically generated Cd(II) ion in a micro-water phase was reacted with 5-octyloxymethyl-8-quinolinol (HC8Q) in 1,6-dichlorohexane. The fluorescence intensity of Cd(C8Q)2 near the water/oil interface (IF) was analyzed under a confocal fluorescence microscope. The rate of decrease of IF was independent of the HC8Q concentration and pH, but was influenced by the phase-boundary potential between the water and oil phases, suggesting that Cd(II) extraction is governed by Cd(C8Q)+ desorption at the interface.

Mass Transfer in Mesoporous Microparticles Studied by Confocal Fluorescence Recovery after Photobleaching.

The intraparticle diffusion of a fluorescent dye in single microparticles in an aqueous solution was analyzed using fluorescence recovery after photobleaching, with a confocal fluorescence microscope. The fluorescence depth profile of single microparticles, and the fluorescence recovery at the particle center, were measured; further, the intraparticle diffusion coefficient was determined through simulations of three-dimensional diffusion in the respective microparticles. The intraparticle diffusion of coumarin 102 in octadecylsilyl silica gel was limited by the surface diffusion.

Analysis of Distribution and Intraparticle Diffusion of a Fluorescent Dye in Mesoporous Silica Gel by Confocal Fluorescence Microspectroscopy.

A micrometer-sized spherical silica gel microparticle (pore diameter, ∼7 nm) was injected into an aqueous rhodamine 6G solution using microcapillary manipulation-injection technique, and the dye distribution in the single microparticle was measured as the fluorescence depth profile by confocal fluorescence microspectroscopy. The fluorescence depth profile was simulated by the convolution and deconvolution methods to correct the contribution of the spatial resolution of the experimental system. The dye homogeneously or heterogeneously distributed in the microparticle at the adsorption equilibrium, dependent on the type of silica gel. The intraparticle diffusion coefficient of the dye distributed homogeneously in the silica gel was analyzed by the simulations of the time dependence of the fluorescence depth profile based on the external and intraparticle diffusion model. The results indicated that the intraparticle diffusion of the dye in the silica gel is governed by the pore diffusion.