Casadó, A;
Mora, M;
Lluïsa Sagristá, M;
Rello-Varona, S;
Acedo, P;
Stockert, JC;
Cañete, M;
(2017)
Improved selectivity and cytotoxic effects of irinotecan via liposomal delivery: A comparative study on Hs68 and HeLa cells.
European Journal of Pharmaceutical Sciences
, 109
pp. 65-77.
10.1016/j.ejps.2017.07.024.
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Abstract
Irinotecan (CPT-11) is an effective chemotherapeutic agent widely used to treat different cancers. Otherwise, the liposomal delivery of anti-tumor agents has been shown to be a promising strategy. The aim of this study has been to analyze the effect of liposomal CPT-11 (CPT-11lip) on two human cell lines (Hs68 and HeLa) to establish the suitability of this CPT-11 nanocarrier. We have demonstrated the highest uptake of CPT-11lip in comparison with that of CPT-11sol, in lactate buffer, and that CPT-11lip was internalized in the cells through an endocytic process whereas CPT-11sol does so by passive diffusion. CPT-11lip was not cytotoxic to normal fibroblast Hs68 cells, but induced a massive apoptosis accompanied by cell senescence in HeLa cells. CPT-11lip treatment modified the morphology of HeLa cells, induced different cell cycle alterations and accumulated into lysosomes in both cell lines. In particular, CPT-11lip treatment showed that surviving HeLa cells remained in a state of senescence whereas only a temporal growth arrest was induced in Hs68 cells. Results of RT-PCR indicated that the different responses in Hs68 (survival) and HeLa cells (apoptotic death), seemed to be induced by a p53- and p53- independent mechanism, respectively. An analysis of DNA damage also determined that released CPT-11 from liposomes was able to reach the nucleus and exert a genotoxic effect in both cell lines, which was repaired in Hs68 but not in HeLa cells. All results indicate that phospholipid-cholesterol liposomes possess optimum properties for CPT-11 delivery, being biocompatible and selectively cytotoxic against HeLa tumorigenic cells..
| Type: | Article |
|---|---|
| Title: | Improved selectivity and cytotoxic effects of irinotecan via liposomal delivery: A comparative study on Hs68 and HeLa cells |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ejps.2017.07.024 |
| Publisher version: | http://doi.org/10.1016/j.ejps.2017.07.024 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Apoptosis, Cytotoxicity, DNA double-strand breaks, Drug uptake, Growth arrest, Irinotecan, Liposomes |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1566740 |
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