Enhanced efficacy of anti-tumor liposomal doxorubicin by hyperthermia.
The efficiency of novel tumor chemotherapeutics could be increased using targeted drug delivery by hyperthermia. In this paper, the 3D liposomal doxorubicin distribution in the tumor tissue enhanced by local hyperthermia was quantitatively studied in real time using laser confocal microscopy. Results showed that the thermally induced liposomal doxorubicin extravasation was non-uniform and more excessive in the peripheral region than that in the tumor center. The effect of the thermally targeted drug delivery was also investigated. On the 1st, 3rd day after the thermally targeted drug treatment, histological examination showed that many nucleolus were condensed and collapsed in the peripheral region. But, in the tumor center, there were no such changes found until the 3rd day. While on the 6th day, tumor cells in both the peripheral and center region were found necrotic. The enhancement of the nanoparticle anti-tumor drug effect was significant. A theoretical analysis of liposomal doxorubicin diffusion to the tumor cells in vivo was performed. Results showed that it took more than 40 hrs for the doxorubicin to get into the tumor cells in the center region from the periphery region. The theoretical results well explained the experimental observations.
Liu
Ping
P
Sch. of Life Sci. & Technol., Shanghai Jiao Tong Univ., PR China.
Xu
Lisa Xuemin
LX
Zhang
Aili
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002466:Cell Nucleolus / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006979:Hyperthermia, Induced; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008962:Models, Theoretical; D009336:Necrosis; D009369:Neoplasms / Q000628:therapy*
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004337:Drug Carriers; D004317:Doxorubicin