In Vitro and In Vivo Therapeutic Evaluation of Camptothecin-Encapsulated β-Cyclodextrin Nanosponges in Prostate Cancer.
Camptothecin (CPT), a pentacyclic alkaloid, is an inhibitor of DNA Topoisomerase-I and shows a wide spectrum of anti-cancer 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 DU145 prostate tumor cell lines, and PC-3 growth in vitro. This work extends these observations by showing that CN-CPT significantly inhibits the 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 delays the growth of 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 in the treatment of prostate cancers.
Casimiro Luca
CL
Gigliotti
Rosalba
R
Minelli
Roberta
R
Cavalli
Sergio
S
Occhipinti
Giuseppina
G
Barrera
Stefania
S
Pizzimenti
Giuseppe
G
Cappellano
Elena
E
Boggio
Laura
L
Conti
Roberto
R
Fantozzi
Mirella
M
Giovarelli
Francesco
F
Trotta
Umberto
U
Dianzani
Chiara
C
Dianzani
D065966:Absorption, Physicochemical; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004058:Diffusion; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D016062:Porosity; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D053769:Nanocapsules; D047392:beta-Cyclodextrins; C031215:betadex; D002166:Camptothecin