A pH-responsive high density lipoprotein-like nanoparticle of epothilone B View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2015-04

AUTHORS

Ji-Chun Lee, Byoung-Jae Kong, Jae Yoon Shin, Jonghyeok Shin, Jung-Su Oh, Jae Youl Cho, Keejung Yoon, Sung-Gun Kim, Young-Ha Song, Chol-Su Shin, Heekyung An, Woo-Jong Lee, Dae-Hyuk Kweon

ABSTRACT

Epothilone B (EpoB) is a paclitaxel (PTX)-like microtubule-stabilizing agent that induces mitotic arrest and apoptosis in cells. EpoB is a promising anti-tumor agent, and is thought to have the potential to overcome well-known PTX resistance. However, EpoB is barely soluble in water, and is fatal to normal cells due to extremely potent cytotoxicity. To reduce the unwanted cytotoxicity of EpoB to normal cells, a reconstituted highdensity lipoprotein (rHDL)-like nanoparticle of EpoB (EpoB-rHDL) was assembled using apolipoprotein A-I (apoA-I). The EpoB-rHDL, as well as PTX-rHDL (a HDLlike nanoparticle of paclitaxel), were indeed mild (nontoxic) to certain cell lines such as MCF7, MDA-MB-231, and SK-OV-3, while free EpoB and PTX were very toxic to those same cells. In contrast, the EpoB-rHDL and PTXrHDL were very effective in killing the Caco-2 and ZR-75-1 while free drugs were less toxic to those cells. The susceptibility of cell lines to rHDLs was dependent on the expression of scavenger receptor class B type I (SR-BI), indicating that EpoB-rHDL selectively and efficiently kills only SR-BI-overexpressing cells. Furthermore, the EpoBrHDL released EpoB only at acidic pH, which may facilitate the escape of drugs from acidic endosome. Thus, EpoB-rHDL shown in this study enables safe and targeted delivery of the potent EpoB to cancer cells in SR-BIdependent manner. More... »

PAGES

249-258

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12257-014-0368-y

DOI

http://dx.doi.org/10.1007/s12257-014-0368-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012757083


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