期刊
JOURNAL OF CONTROLLED RELEASE
卷 209, 期 -, 页码 260-271出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2015.05.007
关键词
Mesenchymal stem cell; Herpes simplex virus thymidine kinase; Ganciclovir; Liposome; Melanoma metastasis; Tumor spheroid
资金
- National Natural Science Foundation of China [81273441, 81473143, 81472818, 81373346]
- Zhejiang Provincial Natural Science Foundation of China [LZ14H300001, Y13H300002]
- National Basic Research Program of China [2014CB931901]
- Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents
- State Scholarship Fund for Tian-Yuan Zhang's studies in Kyoto University in Japan [201306320102]
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. (C) 2015 Elsevier B.V. All rights reserved.
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