title: Enhanced antitumor response mediated by the codelivery of paclitaxel and adenoviral vector expressing IL-12.
abstract: It has been well-established that chemo-immunotherapy using cytotoxic drugs and appropriate cytokines offers a promising approach for the treatment of neoplastic diseases. In view of this, to improve melanoma treatment effect, our study developed a new codelivery system (AL/Ad5/PTX) that paclitaxel (PTX) and adenovirus encoding for murine interleukin-12 (Ad5-mIL-12) were incorporated into anionic liposomes (AL). First, AL/Ad5/PTX complexes were prepared by incorporating Ad5 into anionic PTX liposomes using calcium-induced phase change. Second, the size distribution and zeta potential of AL/Ad5/PTX were investigated. Third, the results of in vitro transduction assays showed that PTX introduced into AL/Ad-luc or AL/Ad5-mIL-12 highly enhanced gene transduction efficiency in B16 cells than naked Ad5 or AL/Ad complexes while it had no comparability in A549 cells. Finally, a melanoma-bearing mouse model was established to assess the antitumor effect. Tumor growth inhibition and prolonged survival time, accompanied by increased mIL-12 or interferon-γ (IFN-γ) expression levels in serum or tumor sites, were observed in mice treated with AL/Ad5-mIL-12/PTX, as compared with those treated with either AL/Ad5-mIL-12 or AL/PTX. In conclusion, these results suggested that codelivery of Ad5-mIL-12 and PTX incorporated into AL could be a relatively efficient strategy for the treatment of melanoma.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, P. R. China.
authors.forename: Linjie
authors.initials: L
authors.lastname: Cao
authors.forename: Qin
authors.initials: Q
authors.lastname: Zeng
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Xu
authors.forename: Sanjun
authors.initials: S
authors.lastname: Shi
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000648:ultrastructure; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use*; D008081:Liposomes / Q000648:ultrastructure; D008297:Male; D008546:Melanoma, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D014161:Transduction, Genetic
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma; D017239:Paclitaxel