Preparation of RGD-modified long circulating liposome loading matrine, and its in vitro anti-cancer effects.
OBJECTIVE
To prepare RGD-modified long circulating liposome (LCL) loading matrine (RGD-M-LCL) to improve the tumor-targeting and efficacy of matrine.


METHODS
LCL which was prepared with HSPC, cholesterol, DSPE-PEG2000 and DSPE-PEG-MAL was modified with an RGD motif confirmed by high performance liquid chromatography (HPLC). The encapsulation efficiency of RGD-M-LCL was also detected by HPLC. MTT assay was used to examine the effects of RGD-M-LCL on the proliferation of Bcap-37, HT-29 and A375 cells. The percentage of apoptotic cells and morphological changes in Bcap-37 cells treated with RGD-M-LCL were detected by Annexin-V-FITC/PI affinity assay and observed under light microscope, respectively.


RESULTS
Spherical or oval single-chamber particles of uniform sizes with little agglutination or adhesion were observed under transmission electronic microscope. The RGD motif was successfully coupled to the DSPE-PEG-MAL on liposomes, as confirmed by HPLC. An encapsulation efficiency of 83.13% was obtained when the drug-lipid molar ratio was 0.1, and the encapsulation efficiency was negatively related to the drug-lipid ratio in the range of 0.1-0.4, and to the duration of storage. We found that, compared with free matrine, RGD-M-LCL had much stronger in vitro activity, leading to anti-proliferative and pro-apoptotic effects against cancer cells (P<0.01).


CONCLUSIONS
RGD-M-LCL, a novel delivery system for anti-cancer drugs, was successfully prepared, and we demonstrated that the use of this material could augment the effects of matrine on cancer cells in vitro.
Liu
Xiao-yan
XY
The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
Ruan
Li-ming
LM
Mao
Wei-wei
WW
Wang
Jin-qiang
JQ
Shen
You-qing
YQ
Sui
Mei-hua
MH
D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D019073:HT29 Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011807:Quinolizines / Q000737:chemistry* / Q000494:pharmacology*; D000093842:Matrines
C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000470:Alkaloids; D000970:Antineoplastic Agents; D008081:Liposomes; D009842:Oligopeptides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011807:Quinolizines; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D000093842:Matrines