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Effective delivery of drug carriers selectively to the kidney is challenging because of their uptake by the reticuloendothelial system in the liver and spleen, which limits effective treatment of kidney diseases and results in side effects. To address this issue, we synthesized L-serine (Ser)-modified polyamidoamine dendrimer (PAMAM) as a potent renal targeting drug carrier. Approximately 82% of the dose was accumulated in the kidney at 3 h after i.v. injection of 111 In-labeled Ser-PAMAM in mice, while i.v. injection of 111 In-labeled unmodified PAMAM, L-threonine modified PAMAM, and L-tyrosine modified PAMAM resulted in kidney accumulations of 28%, 35%, and 31%, respectively. Single-photon emission computed tomography/computed tomography (SPECT/ CT) images also indicated that 111 In-labeled Ser-PAMAM specifically accumulated in the kidneys. An intrakidney distribution study showed that fluorescein isothiocyanate-labeled Ser-PAMAM accumulated predominantly in renal proximal tubules. Results of a cellular uptake study of Ser-PAMAM in LLC-PK1 cells in the presence of inhibitors [genistein, 5-(N-ethyl-N-isopropyl)amiloride, and lysozyme] revealed that caveolae-mediated endocytosis, micropinocytosis, and megalin were associated with the renal accumulation of Ser-PAMAM. The efficient renal distribution and angiotensinconverting enzyme (ACE) inhibition effect of captopril (CAP), an ACE inhibitor, was observed after i.v. injection of the Ser-PAMAM-CAP conjugate. These findings indicate that Ser-PAMAM is a promising renal targeting drug carrier for the treatment of kidney diseases. Thus, the results of this study demonstrate efficient renal targeting of a drug carrier via Ser modification.drug delivery | renal targeting | L-serine | dendrimer

Three kinds of supported cerium oxide catalysts were prepared by an impregnation and a sol–gel technique using aluminium tri-isopropoxide (AIP) and cerium(III) nitrate dissolved in ethylene glycol. One is cerium dioxide supported on alumina, and others are finely-divided nonstoichiometric cerium oxide and cerium aluminate crystallites dispersed on alumina, respectively. In order to investigate the relationship between the structure of cerium oxides and their catalytic behavior, these cerium oxides were subjected to “OSC” (oxygen storage capacity) measurements as well as kinetic studies for methane oxidation. The highest “OSC” was achieved on the finely-divided nonstoichiometric cerium oxides. Kinetics studies for methane oxidation resulted in the first order with respect to methane for all the catalysts, and nearly zero order with respect to oxygen on the cerium dioxide and cerium aluminate. While on the finely-divided nonstoichiometric cerium oxides a half order with respect to oxygen was obtained. On the basis of these results the structure and the catalytic behavior of cerium oxides was discussed in terms of the “OSC” associated with the oxygen vacancies existed in the finely-divided nonstoichiometric cerium oxides. A brief discussion was also made on Pd catalysts supported on these cerium oxides for methane oxidation.

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Mesenchymal stem cells (MSCs) have various functions, making a significant contribution to tissue repair. On the other hand, the viability and function of MSCs are not lasting after an in vivo transplant, and the therapeutic effects of MSCs are limited. Although various chemical modification methods have been applied to MSCs to improve their viability and function, most of conventional drug modification methods are short-term and unstable and cause cytotoxicity. In this study, we developed a method for long-term drug modification to C3H10T1/2 cells, murine mesenchymal stem cells, without any damage, using the avidin-biotin complex method (ABC method). The modification of NanoLuc luciferase (Nluc), a reporter protein, to C3H10T1/2 cells by the ABC method lasted for at least 14 days in vitro without major effects on the cellular characteristics (cell viability, cell proliferation, migration ability, and differentiation ability). Moreover, in vivo, the surface Nluc modification to C3H10T1/2 cells by the ABC method lasted for at least 7 days. Therefore, these results indicate that the ABC method may be useful for long-term surface modification of drugs and for effective MSC-based therapy.

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