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Abstract
Bacteria are highly versatile and useful tools that could deliver short interfering RNA. In this study, a phoP/phoQ double-deleted Salmonella Typhimurium named VNP(PhoP/Q−) based on the genetic background of VNP20009. The biological safety and function of VNP(PhoP/Q−) were also analyzed. Our study revealed the following results: (1) VNP(PhoP/Q−) exhibited lower titers in tumor-free livers and spleens than VNP20009, (2) The survival of VNP(PhoP/Q−) in macrophages and 4T1 tumor cells was significantly reduced compared with that of VNP20009, (3) The tumor-targeting ability of VNP(PhoP/Q−) was significantly enhanced compared with that of VNP20009, and the anticancer effects of VNP(pPhoP/Q−) and VNP20009 on tumor-bearing mice were similar, (4) VNP(PhoP/Q−) could release an shRNA-expressing plasmid and express the EGFP reporter gene in tumor tissue. Therefore, VNP(PhoP/Q−) exhibited a better safety level in tumor-free mice and elicited an anti-tumor effect on tumor-bearing mice. Moreover, VNP(PhoP/Q−) could release an shRNA-expressing plasmid into the cytoplasm of host cells to silence targeted genes.
Disclosure of Potential Conflicts of Interest
The authors declare that they have no conflict of interest.
Acknowledgments
The authors are grateful to grants from the Ministry of Science and Technology (2012CB967004, 2014CB744501, 2012AA020809, and 2012ZX09401012), the Doctoral Station Science Foundation from the Chinese Ministry of Education (20130091130003), the Chinese National Natural Sciences Foundation (81121062), the Jiangsu Provincial Nature Science Foundation (BZ2012050 and BE2013630), and the Bureau of Science and Technology of Changzhou (CZ20130011, CE20135013, CZ20120004, CM20122003, and WF201207).