Nanosponge-encapsulated camptothecin exerts anti-tumor activity in human prostate cancer cells.
Camptothecin (CPT) is a potent DNA Topoisomerase I inhibitor with anti-tumor activity in hematological and solid tumors. However, it did not reach clinical use because of its poor solubility and high degrability. β-Cyclodextrin nanosponge (CN) have been demonstrated to be able to increase the solubility of lipophilic compounds and to protect them from degradation. In the present study, we evaluated whether β-Cyclodextrin nanosponge carriers can overcome CPT chemical disadvantages and improve the in vitro anti-tumor efficacy in the androgen refractory models of prostate cancer DU145 and PC-3 and the androgen sensitive model LNCaP. Camptothecin-loaded β-Cyclodextrin nanosponge (CN-CPT) showed sizes of about 400 nm, spherical shape and a drug loading of 38%. HPLC analysis, performed on the cell pellet after treatment with CN-CPT revealed that CPT concentration increased over time indicating a prolonged release of the drug. Moreover, CN-CPT inhibited Topoisomerase I activity, and induced DNA damage, and cell cycle arrest more effectively than CPT, indicating that the CN-CPT formulation does not affect activity of the drug. Moreover, Annexin V/Propidium Iodide staining showed an induction of cell death at low concentrations that were not effective for CTP. LNCaP cells were less sensitive to CPT than PC-3 and DU145 cells, but CN-CPT still exerted higher anti-proliferative activity and DNA damage ability than CPT. The experiments performed in LNCaP cells demonstrated that CN-CPT treatment inhibited expression of the androgen receptor at doses where CPT was ineffective. Our results demonstrated the higher anti-tumor effectiveness of CN-CPT compare to CPT in prostate cancer cells, supporting the relevance of future studies for the use of the β-Cyclodextrin nanosponge to deliver anticancer drugs in vivo.
Department of Drug Science and Technology, University of Turin, Via P. Giuria 9, 10125 Turin, Italy.
Rosalba
R
Minelli
Roberta
R
Cavalli
Leigh
L
Ellis
Piergiorgio
P
Pettazzoni
Francesco
F
Trotta
Eric
E
Ciamporcero
Giuseppina
G
Barrera
Roberto
R
Fantozzi
Chiara
C
Dianzani
Roberto
R
Pili
D000728:Androgens / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D002166:Camptothecin / Q000008:administration & dosage* / Q000737:chemistry*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004249:DNA Damage / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012995:Solubility; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry*
D000728:Androgens; D000970:Antineoplastic Agents; D004337:Drug Carriers; D006657:Histones; D059004:Topoisomerase I Inhibitors; D047392:beta-Cyclodextrins; D002166:Camptothecin