Hyperthermia-induced antitumor activity of thermosensitive polymer modified temperature-sensitive liposomes.
Temperature-sensitive liposomes (TS-liposomes) have been studied for chemotherapeutic purposes to enhance the release of anticancer drugs at tumor sites. In this study, we prepared poly(N-isopropylacrylamide-co-acrylamide) (PNIPAM-AAM) and polyethylene glycol (PEG)-modified TS-liposomes (PETS-liposomes). PETS-liposomes significantly increased in vitro drug release in serum compared with PEG-fixed or PNIPAM-AAM-modified liposomes. Furthermore, incorporation of both PNIPAM-AAM and PEG into PETS-liposomes enhanced the stabilities of liposomes in serum by inhibiting protein adsorption. In addition, to investigate the therapeutic efficacy of doxorubicin (DOX)-loaded PETS-liposomes, the in vivo antitumor activity of liposomes in combination with hyperthermia was evaluated in a B16F10 melanoma tumor-bearing mouse model. PETS-liposomes showed much higher levels of tumor growth inhibition than PEG-fixed or PNIPAM-AAM-modified TS-liposomes. Moreover, the antitumor activity of PETS-liposomes was enhanced significantly when they were administered in combination with hyperthermia. PETS-liposomes were found to be highly efficacious carriers for the in vivo delivery of anticancer drugs, and to have potential anticancer applications in combination with hyperthermia.
Han
Hee Dong
HD
Medicinal Science Division, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong, Daejeon 305-600, South Korea.
Choi
Min Soo
MS
Hwang
Taewon
T
Song
Chung Kil
CK
Seong
Hasoo
H
Kim
Tae Woo
TW
Choi
Ho Suk
HS
Shin
Byung Cheol
BC
D000180:Acrylic Resins; D000327:Adsorption; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001798:Blood Proteins / Q000737:chemistry; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D004337:Drug Carriers; D005079:Excipients; D005334:Fever / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011092:Polyethylene Glycols; D011108:Polymers; D013696:Temperature
D000180:Acrylic Resins; D000970:Antineoplastic Agents; D001798:Blood Proteins; D004337:Drug Carriers; D005079:Excipients; D008081:Liposomes; D011108:Polymers; C052970:poly-N-isopropylacrylamide; D011092:Polyethylene Glycols