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

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.