title: Liposome-based co-delivery of siRNA and docetaxel for the synergistic treatment of lung cancer.
abstract: Combination of more than one therapeutic strategy is the standard treatment in clinics. Co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) within a nanoparticulate system will suppress the tumor growth. In the present study, docetaxel (DTX) and BCL-2 siRNA was incorporated in a PEGylated liposome to systemically deliver in a lung cancer model (A549). The resulting nanoparticle (lipo-DTX/siRNA) was stable and exhibited a sustained release profile. The co-delivery of therapeutic moieties inhibited the cell proliferation (A549 and H226) in a time-dependent manner. Moreover, the co-delivery system of DTX and siRNA exhibited a remarkable apoptosis of cancer cells with elevated levels of caspase 3/7 activity (apoptosis markers). Cell cycle analysis further showed remarkable increase in sub-G0/G1 phase, indicating increasing hypodiploids or apoptotic cells. Pharmacokinetic study showed a long circulating profile for DTX from lipo-DTX/siRNA system facilitating the passive tumor targeting. In vivo antitumor study on A549 cell bearing xenograft tumor model exhibited a remarkable tumor regression profile for lipo-DTX/siRNA with 100% survival rate. The favorable tumor inhibition response was attributed to the synergistic effect of DTX potency and MDR reversing ability of BCL-2 siRNA in the tumor mass. Overall, experimental results suggest that co-delivery of DTX and siRNA could be promising approach in the treatment of lung cancers.
authors.affiliation: Department of Medicinal Oncology, The Third People's Hospital Of Dalian, Dalian 116033, China.
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Qu
authors.affiliation: Department of Medicinal Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Rui-Fang
authors.initials: RF
authors.lastname: Zeng
authors.affiliation: Department of Clinical Nutrition, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Medicinal Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Qiang-Sheng
authors.initials: QS
authors.lastname: Dai
authors.affiliation: Department of Medicinal Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Li
authors.affiliation: Department of Medicinal Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China. Electronic address: longjianting258@gmail.com.
authors.forename: Jian-Ting
authors.initials: JT
authors.lastname: Long
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D008081:Liposomes; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D034741:RNA, Small Interfering; D043823:Taxoids; D000077143:Docetaxel
keywords: Antitumor; Docetaxel; Liposomes; Lung cancer; siRNA