Abstract
Nonviral gene transfection overcomes some of the disadvantages of viral vectors, such as undesired immune responses, safety concerns, issues relating to bulk production, payload capacity, and quality control, but generally have low transfection efficiency. Here we describe the effects of a modified form of photodynamic therapy (PDT), i.e., photochemical internalization (PCI) to: (1) greatly increase nonviral cytosine deaminase gene (CD) transfection into tumor cells, significantly increasing the conversion of 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU), and (2) enhance the toxic efficacy of the locally produced 5-FU to induce cell death on both transfected and non-transfected bystander cells.
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References
Mullen CA, Coale MM, Lowe R, Blaese RM (1994) Tumors expressing the cytosine-deaminase suicide gene can be eliminated in vivo with 5-fluorocytosine and induce protective immunity to wild-type tumor. Cancer Res 54:1503–1506
Miller RC, Williams CR, Buchsbaum DJ, Gillespie GY (2002) Intratumoral 5-fluorouracil produced by cytosine deaminase/5-fluorocytosine gene therapy is effective for experimental human glioblastomas. Cancer Res 62:773–780
Johnson AJ, Ardiani A, Sanchez-Bonilla M, Black ME (2011) Comparative analysis of enzyme and pathway engineering strategies for 5FC-mediated suicide gene therapy applications. Cancer Gene Ther 18:533–542
Berg K, Berstad M, Prasmickaite L, Weyergang A, Selbo PK, Hedfors I, Høgset A (2010) Photochemical internalization (PCI): a new tool for gene and oligonucleotide delivery. Top Curr Chem 296:251–281
Prasmickaite L, Høgset A, Olsen VM, Kaalhus O, Mikalsen SO, Berg K (2004) Photochemically enhanced gene transfection increases the cytotoxicity of the herpes simplex virus thymidine kinase gene combined with ganciclovir. Cancer Gene Ther 11:514–523
Wang F, Zamora G, Sun CH, Trinidad A, Chun C, Kwon YJ, Berg K, Madsen SJ, Hirschberg H (2014) Increased sensitivity of glioma cells to 5-fluorocytosine following photo-chemical internalization enhanced nonviral transfection of the cytosine deaminase suicide gene. J Neurooncol 118(1):29–37
Zamora G, Wang F, Sun CH, Trinidad A, Kwon YJ, Cho SK, Berg K, Madsen SJ, Hirschberg H (2014) Photochemical internalization-mediated nonviral gene transfection: polyamine core-shell nanoparticles as gene carrier. J Biomed Opt 19(10):105009
Christie C, Pomeroy A, Nair R, Berg K, Hirschberg H (2017) Photodynamic therapy enhances the efficacy of gene-directed enzyme prodrug therapy. Photodiagnosis Photodyn Ther 18:140–148
Madsen SJ, Sun CH, Tromberg BJ, Cristini V, De Magalhães N, Hirschberg H (2006) Multicell tumor spheroids in photodynamic therapy. Lasers Surg Med 38:555–564
Liu J, Guo S, Li Z, Liu L, Gu J (2009) Synthesis and characterization of stearyl protamine and investigation of their complexes with DNA for gene delivery. Colloids Surf B Biointerfaces 73:36–41. https://doi.org/10.1016/j.colsurfb.2009.04.026
Acknowledgments
This work is supported by grants from the Norwegian Radium Hospital Research Foundation. Portions of this study were made possible through access to the Laser Microbeam and Medical Program (LAMMP) at the University of California, Irvine.
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Sun, CH., Berg, K., Hirschberg, H. (2019). Photochemical Internalization Enhanced Nonviral Suicide Gene Therapy. In: Düzgüneş, N. (eds) Suicide Gene Therapy. Methods in Molecular Biology, vol 1895. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8922-5_13
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DOI: https://doi.org/10.1007/978-1-4939-8922-5_13
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