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• W2059978839 abstract "PEGylated polyplexes (lac-PEGylated polyplexes) composed of poly(L-lysine) and lactosylated poly(ethylene glycol)-small interfering RNA conjugate, which inhibits the RecQL1 gene product, were revealed to show an appreciable growth inhibition of multicellular HuH-7 spheroids (human hepatocarcinoma cell lines) for up to 21 days (IC50=6 nM); this system used as an in vitro three-dimensional (3D) model mimicking the in vivo biology of tumors. The PEGylated polyplexes thus prepared had a size of approximately 110 nm with clustered lactose moieties on their periphery as targeting ligands for the asialoglycoprotein-receptor-expressing HuH-7 cells. In contrast, OligofectAMINE/siRNA (cationic lipoplex) was observed to have almost no growth-inhibitory effect against HuH-7 spheroids, even though the lipoplex showed a stronger growth-inhibitory effect than the lac-PEGylated polyplexes on conventional monolayer-cultured HuH-7 cells. The FITC-tagged conjugate in the lac-PEGylated polyplexes showed smooth penetration into the HuH-7 spheroids compared with that in the lipoplexes, as observed by confocal fluorescence-scanning microscopy. This indicates that the small size of approximately 100 nm and the reduced nonspecific interaction due to the nonionic and hydrophilic lactosylated PEG layer contributes to the smooth penetration of the PEGylated polyplexes into the spheroid interior, eventually facilitating their uptake into the cells composing the spheroids. Cellular apoptosis indicating programmed cell death was also observed in the HuH-7 spheroids treated with the PEGylated polyplexes, revealing that the observed growth inhibition was indeed induced by the RNAi of the RecQL1 siRNA. These data suggest that the smart PEGylated polyplexes can indeed penetrate into the multiple cell layers of 3D tumor masses in vivo, exerting therapeutic effects through the RNAi." @default.
• W2059978839 created "2016-06-24" @default.
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• W2059978839 date "2007-09-10" @default.
• W2059978839 modified "2023-10-18" @default.
• W2059978839 title "Enhanced Growth Inhibition of Hepatic Multicellular Tumor Spheroids by Lactosylated Poly(ethylene glycol)-siRNA Conjugate Formulated in PEGylated Polyplexes" @default.
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• W2059978839 doi "https://doi.org/10.1002/cmdc.200700076" @default.
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