Journal d'imagerie et de dynamique moléculaires
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Abstrait

Controlled Molecular Targeting of Inducible Heat Shock Proteins

Pradip Ghosh, Jan AL. Lammel, Tae Hoon Lee, Xukui Wang and Daniel Y. Lee

In an effort to devise schemes to site-specifically deliver drugs “on demand” we have leveraged the inducible expression properties of the well-characterized class of stress-response factors, the heat shock proteins. We asked whether a small molecule ligand selective for such proteins could be used as a potential theranostic platform. By conjugating a fluorescent dye to a recently identified nucleoside analog with modest affinity for heat shock protein 70 (HSP70), we have found that cellular uptake can be enhanced following transient heat shock in vitro. The in vivo performance of this compound was further evaluated in nude mice subjected to locoregional hyperthermia which showed a modest level of accumulation in the treated muscle. This effect correlates with relative levels of HSP70 over expression in the treated tissue, supporting the hypothesis that molecular targeting can be enhanced by inducing endogenous proteins through external means.