Anti-tumor activity of biodegradable polymer-paclitaxel conjugate micelles on Lewis lung cancer mice models.
Two kinds of paclitaxel (PTX) conjugate nanomicelles were prepared for cell apoptosis and anti-tumor activity evaluation on Lewis lung cancer mice models. One (PTX micelles) was prepared by self-assembling the PTX-conjugate co-polymer, poly(ethylene glycol)-b-poly(L-lactide-co-2-methyl-2-carboxyl-propylene carbonate/PTX), and the other (FA-PTX micelles) was by co-assembling a mixture of the folic acid (FA)-carrying co-polymer poly(ethylene glycol)-b-poly(L-lactide-co-2,2-dihydroxylmethyl-propylene carbonate/FA) (PEG-b-P(LA-co-DHP/FA)), and the PTX-conjugate co-polymer. At 7 and 14 days after tail intravenous injection, the mice were killed. The inhibition rates of tumor growth for PTX and FA-PTX micelles were 50 and 90%, respectively, on the day 7, and 33 and 71%, respectively, on the day 14 after drug injection. Flow cytometry analysis showed that the cell apoptosis rates were 43, 54 and 72% for the control group, PTX micelles group and FA-PTX micelles group, respectively, on the day 7, and 16, 25 and 42 on the day 14. With the TUNEL assay, the grey values of PTX micelles and FA-PTX micelles groups were determined to be 61-62% and 43-44%, of that of the control group, on day 7 or day 14, respectively. Therefore, the PTX micelles and the FA-PTX composite micelles significantly inhibited the subcutaneously inoculated Lewis lung cancer and effectively induced the cell apoptosis, and the FA-PTX composite micelles displayed a better efficacy than the PTX-micelles, implying the contribution of the folate-mediated targeting and endocytosis effect.
Wan
Yanhui
Y
a The First Hospital, Jilin University, Changchun 130021, P. R. China.
Zheng
Yonghui
Y
Song
Xiangfu
X
Hu
Xiuli
X
Liu
Shi
S
Tong
Ti
T
Jing
Xiabin
X
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D005492:Folic Acid / Q000737:chemistry; D007275:Injections, Intravenous; D008810:Mice, Inbred C57BL; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage*; D011108:Polymers / Q000737:chemistry; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D005492:Folic Acid; D017239:Paclitaxel