title: Synergistic effects of co-administration of suicide gene expressing mesenchymal stem cells and prodrug-encapsulated liposome on aggressive lung melanoma metastases in mice.
abstract: The success of conventional suicide gene therapy for cancer treatment is still limited because of lack of efficient delivery methods, as well as poor penetration into tumor tissues. Mesenchymal stem cells (MSCs) have recently emerged as potential vehicles in improving delivery issues. However, these stem cells are usually genetically modified using viral gene vectors for suicide gene overexpression to induce sufficient therapeutic efficacy. This approach may result in safety risks for clinical translation. Therefore, we designed a novel strategy that uses non-viral gene vector in modifying MSCs with suicide genes to reduce risks. In addition, these cells were co-administrated with prodrug-encapsulated liposomes for synergistic anti-tumor effects. Results demonstrate that this strategy is effective for gene and prodrug delivery, which co-target tumor tissues, to achieve a significant decrease in tumor colonization and a subsequent increase in survival in a murine melanoma lung metastasis model. Moreover, for the first time, we demonstrated the permeability of MSCs within tumor nests by using an in vitro 3D tumor spheroid model. Thus, the present study provides a new strategy to improve the delivery problem in conventional suicide gene therapy and enhance the therapeutic efficacy. Furthermore, this study also presents new findings to improve our understanding of MSCs in tumor-targeted gene delivery.
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Tian-Yuan
authors.initials: TY
authors.lastname: Zhang
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Huang
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Wu
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Jia-He
authors.initials: JH
authors.lastname: Wu
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Li
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Yan-Xin
authors.initials: YX
authors.lastname: Li
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Hu
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Han
authors.affiliation: Center for Bionanoengineering and State Key Laboratory of Chemical Engineering, Zhejiang University, Hangzhou, PR China.
authors.forename: You-Qing
authors.initials: YQ
authors.lastname: Shen
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China. Electronic address: gaojianqing@zju.edu.cn.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Gao
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D015774:Ganciclovir / Q000008:administration & dosage / Q000737:chemistry; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D008081:Liposomes; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy*; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D008810:Mice, Inbred C57BL; D011355:Prodrugs / Q000008:administration & dosage; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D008081:Liposomes; D011355:Prodrugs; D013937:Thymidine Kinase; D015774:Ganciclovir
keywords: Ganciclovir; Herpes simplex virus thymidine kinase; Liposome; Melanoma metastasis; Mesenchymal stem cell; Tumor spheroid