Synergistic treatment of ovarian cancer by co-delivery of survivin shRNA and paclitaxel via supramolecular micellar assembly.
Non-viral gene-delivery platforms have been developed to co-deliver chemotherapeutics and siRNAs. The synergistic effects between shRNAs against survivin and Paclitaxel (PTX) using supramolecular micelles self-assembled from the host PEI-CyD (PC) composed of β-cyclodextrin (β-CyD) and polyethylenimine (PEI, Mw 600) and guest adamantine conjugated PTX (Ada-PTX) in combination cancer therapy are investigated. The Ada-PTX is encapsulated inside the core and shRNA sticks to the shell surface. The physicochemical properties of these supramolecular nanoparticles are favorable to cell uptake and intracellular trafficking. Moreover, PTX and shRNA simultaneously delivered to SKOV-3 cells lead to efficient reduction in the survivin and Bcl-2 expression as well as synergistic cell apoptotic induction in the in vitro study. In particular, co-delivery of survivin shRNA and PTX suppresses cancer growth more effectively than delivery of either paclitaxel or shRNA in ovarian cancer therapy.
Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, PR China.
Qinglian
Q
Hu
Wen
W
Li
Xiurong
X
Hu
Qida
Q
Hu
Jie
J
Shen
Xue
X
Jin
Jun
J
Zhou
Guping
G
Tang
Paul K
PK
Chu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000378:metabolism; D000077022:Survivin; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000138:chemical synthesis / Q000737:chemistry
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008823:Micelles; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D000077022:Survivin; D047392:beta-Cyclodextrins; D011094:Polyethyleneimine; C031215:betadex; D017239:Paclitaxel