Camptothecin (CPT), a pentacyclic alkaloid, is aninhibitor of DNA Topoisomerase-I and shows a wide spectrum of anticancer activities. The use of CPT has been hampered by poor aqueous solubility and a high degradation rate. Previously, it has been reported that CPT encapsulated in β-cyclodextrin-nanosponges(CN-CPT) overcomes these disadvantages and improves the CPT’s inhibitory effect on the prostate tumor cell lines DU145, and PC-3 growth in vitro. This work extends these observations showing that CN-CPT significantly inhibits adhesion and migration of these tumor cells and their STAT3 phosphorylation. The anti-adhesive effect is exerted also in human endothelial cells, in which CN-CPT also inhibits the angiogenic activity as assessed by the tubulogenesis and sprouting assays. Finally, CN-CPT substantially delayed PC-3 cell engraftment in SCID mice in vivo without apparent toxic effects. These results support the use of β-cyclodextrin nanosponge nanotechnology as a potential nanocarrier for delivery of anticancer drugs for the treatment of prostate cancers.

In Vitro and In Vivo Therapeutic Evaluation of Camptothecin-Encapsulated β-Cyclodextrin Nanosponges in Prostate Cancer

MINELLI, ROSALBA;CAVALLI, Roberta;OCCHIPINTI, SERGIO;BARRERA, Giuseppina;PIZZIMENTI, Stefania;CONTI, Laura;FANTOZZI, Roberto;GIOVARELLI, Mirella;TROTTA, Francesco;DIANZANI, Chiara
Last
2016-01-01

Abstract

Camptothecin (CPT), a pentacyclic alkaloid, is aninhibitor of DNA Topoisomerase-I and shows a wide spectrum of anticancer activities. The use of CPT has been hampered by poor aqueous solubility and a high degradation rate. Previously, it has been reported that CPT encapsulated in β-cyclodextrin-nanosponges(CN-CPT) overcomes these disadvantages and improves the CPT’s inhibitory effect on the prostate tumor cell lines DU145, and PC-3 growth in vitro. This work extends these observations showing that CN-CPT significantly inhibits adhesion and migration of these tumor cells and their STAT3 phosphorylation. The anti-adhesive effect is exerted also in human endothelial cells, in which CN-CPT also inhibits the angiogenic activity as assessed by the tubulogenesis and sprouting assays. Finally, CN-CPT substantially delayed PC-3 cell engraftment in SCID mice in vivo without apparent toxic effects. These results support the use of β-cyclodextrin nanosponge nanotechnology as a potential nanocarrier for delivery of anticancer drugs for the treatment of prostate cancers.
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Gigliotti, Casimiro Luca; Minelli, Rosalba; Cavalli, Roberta; Occhipinti, Sergio; Barrera, Giuseppina; Pizzimenti, Stefania; Cappellano, Giuseppe; Boggio, Elena; Conti, Laura; Fantozzi, Roberto; Giovarelli, Mirella; Trotta, Francesco; Dianzani, Umberto; Dianzani, Chiara
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1532157
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