Dual-targeting daunorubicin liposomes improve the therapeutic efficacy of brain glioma in animals.
Chemotherapy for brain glioma has been of limited value due to the inability of transport of drug across the blood-brain barrier (BBB) and poor penetration of drug into the tumor. For overcoming these hurdles, the dual-targeting daunorubicin liposomes were developed by conjugating with p-aminophenyl-alpha-D-manno-pyranoside (MAN) and transferrin (TF) for transporting drug across the BBB and then targeting brain glioma. The dual-targeting effects were evaluated on the BBB model in vitro, C6 glioma cells in vitro, avascular C6 glioma tumor spheroids in vitro, and C6 glioma-bearing rats in vivo, respectively. After applying dual-targeting daunorubicin liposomes, the transport ratio across the BBB model was significantly increased up to 24.9%. The most significant uptake by C6 glioma was evidenced by flow cytometry and confocal microscope. The C6 glioma spheroid volume ratio was significantly lowered to 54.7%. The inhibitory rate to C6 glioma cells after crossing the BBB was significantly enhanced up to 64.0%. The median survival time of tumor bearing rats after administering dual-targeting daunorubicin liposomes (22 days) was significantly longer than that after giving free daunorubicin (17 days, P=0.001) or other controls. In conclusion, the dual-targeting daunorubicin liposomes are able to improve the therapeutic efficacy of brain glioma in vitro and in animals.
State Key Laboratory of Natural and Biomimetic Drugs, and School of Pharmaceutical Sciences, Peking University, Beijing, China.
Xue
X
Ying
He
H
Wen
Wan-Liang
WL
Lu
Ju
J
Du
Jia
J
Guo
Wei
W
Tian
Ying
Y
Men
Yan
Y
Zhang
Ruo-Jing
RJ
Li
Ting-Yuan
TY
Yang
De-Wei
DW
Shang
Jin-Ning
JN
Lou
Liang-Ren
LR
Zhang
Qiang
Q
Zhang
D000814:Aniline Compounds / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003630:Daunorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004337:Drug Carriers; D005434:Flow Cytometry; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008081:Liposomes; D008297:Male; D008362:Mannosides / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D051381:Rats; D017207:Rats, Sprague-Dawley; D018874:Spheroids, Cellular; D013997:Time Factors; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism*
D000814:Aniline Compounds; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D008362:Mannosides; D014168:Transferrin; C034056:4-aminophenylmannoside; D003630:Daunorubicin