Functionalized graphene oxide-based thermosensitive hydrogel for magnetic hyperthermia therapy on tumors.
A novel locally injectable, biodegradable, and thermo-sensitive hydrogel made from chitosan and β-glycerophosphate salt was prepared. It incorporated polyethylenimine (PEI)-modified super-paramagnetic graphene oxide (GO/IONP/PEI) as a form of minimally invasive treatment of cancer lesions by magnetically induced local hyperthermia. Doxorubicin (DOX) was mixed into the hydrogel which was pre-loaded on GO/IONP/PEI to create a drug delivery system DOX-GO/IONP/PEI-gel. In addition to the evaluation of in vitro and in vivo antitumor activities, the physicochemical properties, magnetic properties and DOX release profile of the DOX-GO/IONP/PEI-gel were determined. The aqueous solution of the hydrogel showed a sol-gel transition behavior depending on temperature changes. Magnetization loops indicated the super-paramagnetic properties of GO/IONP/PEI. Compared with free DOX, DOX-GO/IONP/PEI could efficiently pass through cell membranes, leading to more apoptosis and demonstrating higher antitumor efficacy on MCF-7 cells in vitro. Furthermore, DOX-GO/IONP/PEI-gel intratumorally injected (i.t.) showed high antitumor efficacy on tumor-bearing mice in vivo, with no obvious toxicity. The antitumor efficacy was higher when combined with an alternating magnetic field (AMF), showing that DOX-GO/IONP/PEI-gel under AMF has great potential for cancer magnetic hyperthermia therapy.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, People's Republic of China. Pharmacy College, Henan University of TCM, Zhengzhou, 450003, People's Republic of China.
Xiali
X
Zhu
Huijuan
H
Zhang
Heqing
H
Huang
Yingjie
Y
Zhang
Lin
L
Hou
Zhenzhong
Z
Zhang
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000628:therapy*; D048271:Chitosan / Q000737:chemistry; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005994:Glycerophosphates / Q000737:chemistry; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry; D006979:Hyperthermia, Induced / Q000379:methods*; D061986:MCF-7 Cells; D060526:Magnetic Fields; D051379:Mice; D011094:Polyethyleneimine / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D005994:Glycerophosphates; D020100:Hydrogels; D006108:Graphite; D004317:Doxorubicin; D011094:Polyethyleneimine; D048271:Chitosan; C031463:beta-glycerophosphoric acid