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• W2273997948 abstract "C124 Drug delivery systems can improve the pharmacological profiles of anticancer agents. Currently available nanoscale drug delivery systems e.g. liposomes, cationic polymers, dendrimers and polymer-drug conjugates suffer from inherent limitations such as instability or polydisperse size distribution, often resulting in nonspecific accumulation and toxicity to normal organs. We have developed silica nanotubes, an advanced delivery system where size, size distribution, functionalization and drug loading capacity can be precisely tuned to enable a higher degree of control over the biological fate. Nanotubes have several advantages: first, their inner voids can be used to load large amounts of drug molecules and their open ends can be used as a gate to control drug release. Secondly, differential functionalization can allow selective attachment of moieties to the inside (drugs, diagnostic agents) and outside (targeting moieties). Thirdly they are mechanically robust with no swelling or porosity changes under physiological conditions. By loading drugs inside the tubes, the outer surface can be kept biocompatible which can prevent aggregation and non-specific adsorption.
 In this study we examined the toxicity of silica nanotubes with a positive and negative charge and at particle sizes of 200 nm and 500 nm respectively. For in vitro cytotoxicity studies, the nanotubes were empty, for in vivo nude mouse studies, the nanotubes were loaded with AlexaFlour 488. In vitro MTT cell proliferation assays were performed with HEK293T embryonic kidney cells that were treated with nanotubes for 72 hours in concentrations ranging from 0.005 to 5 µg/mL. In vivo tolerability and biodistribution studies were done with 500 nm nanotubes in tumor bearing nude mice. 105 to 3x109 nanotubes were injected intravenously (i.v.) and animals sacrificed 30 min. to 48 hrs after i.v. injection for cyrosectioning and fluorescence imaging of tissues (tumor, spleen, liver, kidney).
 Nanotubes did affect the growth of HEK293T cells in a concentration and size dependent manner. Particle sizes of 200 nm (IC50 >0.05 µg/mL) were more cytotoxic than 500 nm (IC50 >0.5 µg/mL). Negatively charged 500 nm silica nanotubes however, were not toxic to HEK293T kidney cells, even at 0.5 µg/mL suggesting a differential uptake. In mice, both positive and negatively charged 500 nm nanotubes were tolerated at up to 3x109 particles per mouse (~ 0.5 µg/mL). Fluorescent nanotubes were detected in spleen and tumor, but not liver and kidney. The charge of the nanotubes appeared to have no influence on their biodistribution. A detailed time course of AlexaFlour 488 uptake will be presented.
 Our data suggest that silica nanotubes are tolerated by normal cells and organs in mice, and could be used to target anticancer agents to tumors. However, further functionalization is needed to reduce normal tissue accumulation." @default.
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• W2273997948 date "2007-11-01" @default.
• W2273997948 modified "2023-09-24" @default.
• W2273997948 title "Biological evaluation of silica nanotubes for targeted drug delivery" @default.
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