Enhanced antitumor effect of novel dual-targeted paclitaxel liposomes.
A novel dual-targeted peptide containing an alpha V integrins specific ligand and a neuropilin-1 specific motif was developed which showed an increased specific targeting affinity to tumors. Active dual-targeted liposomes were then produced with this peptide and exhibited greater binding activity than single-targeted liposomes in vitro. Paclitaxel entrapped in this formulation greatly increased the uptake of paclitaxel in the targeting cells and significantly suppressed the growth of HUVEC and A549 cells compared with general paclitaxel injections (Taxol) and single-targeted paclitaxel liposomes. The treatment of tumor xenograft models with dual-targeted paclitaxel liposomes also resulted in better tumor growth inhibition than any other treatment groups. Therefore, the dual-targeted paclitaxel liposomes prepared in the present study might be a more promising drug for cancer treatment. Furthermore, the dual-targeting approach may produce synergistic effects that can be applied in the development of new targeted drug delivery systems.
Meng
Shuyan
S
Cancer Institute of Tongji University School of Medicine, Shanghai Pulmonary Hospital, Shanghai, People's Republic of China.
Su
Bo
B
Li
Wei
W
Ding
Yongmei
Y
Tang
Liang
L
Zhou
Wei
W
Song
Yin
Y
Li
Heyan
H
Zhou
Caicun
C
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D017239:Paclitaxel / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D008081:Liposomes; D010455:Peptides; D016650:Fluorescein-5-isothiocyanate; D017239:Paclitaxel