Liposome encapsulation reduces cantharidin toxicity.
Several reports have demonstrated that cantharidin is a strong anticancer compound in vitro; however, its in vivo usefulness is often limited due to its high systemic toxicity. In this study, we encapsulated cantharidin into pegylated liposomes and studied its activity against human breast cancer MCF-7 cells in vitro and its systemic toxicity in mice. Another two methods were also used to reduce the dosage of cantharidin, including labeling liposomal cantharidin with octreotide and exposing cells to hyperbaric oxygen. The cytotoxic activity of pegylated liposomal cantharidin was drastically reduced compared with free cantharidin in vitro. Octreotide-labeled pegylated liposomal cantharidin induced cell death by specifically targeting somatostatin receptors in MCF-7 cells. Cell death was augmented with a low dose of cantharidin under hyperbaric oxygen. Liposomal cantharidin had significantly less systemic toxicity than free cantharidin in vivo and also exhibited a high efficacy against antitumor growth in nude mice. These results suggest that the systemic toxicity of cantharidin can be mitigated by liposome encapsulation; however, that did not decrease its antitumor activity.
Chang
Chun-Chao
CC
Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
Liu
Der-Zen
DZ
Lin
Shyr-Yi
SY
Liang
Hong-Jen
HJ
Hou
Wen-Chi
WC
Huang
Wei-Jan
WJ
Chang
Chih-Hsiang
CH
Ho
Feng-Ming
FM
Liang
Yu-Chih
YC
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity*; D002193:Cantharidin / Q000008:administration & dosage* / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D004339:Drug Compounding; D004563:Electrochemistry; D005260:Female; D006801:Humans; D006931:Hyperbaric Oxygenation; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015282:Octreotide / Q000138:chemical synthesis; D010316:Particle Size; D013778:Tetrazolium Salts; D013844:Thiazoles
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D002193:Cantharidin; D015282:Octreotide