期刊
JOURNAL OF BIOMEDICAL OPTICS
卷 19, 期 10, 页码 -出版社
SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
DOI: 10.1117/1.JBO.19.10.105009
关键词
photochemical internalization; photodynamic therapy; nanoparticles; gene therapy; nonviral gene transfection; brain tumor
资金
- Norwegian Radium Hospital Research Foundation
- Chao Family Comprehensive Cancer Center, University of California, Irvine
- National Cancer Institute of the National Institutes of Health [P30CA062203]
The overall objective of the research was to investigate the utility of photochemical internalization (PCI) for the enhanced nonviral transfection of genes into glioma cells. The PCI-mediated introduction of the tumor suppressor gene phosphatase and tensin homolog (PTEN) or the cytosine deaminase (CD) pro-drug activating gene into U87 or U251 glioma cell monolayers and multicell tumor spheroids were evaluated. In the study reported here, polyamine-DNA gene polyplexes were encapsulated in a nanoparticle (NP) with an acid degradable polyketal outer shell. These NP synthetically mimic the roles of viral capsid and envelope, which transport and release the gene, respectively. The effects of PCI-mediated suppressor and suicide genes transfection efficiency employing either naked polyplex cores alone or as NP-shelled cores were compared. PCI was performed with the photosensitizer AlPcS2a and. lambda = 670-nm laser irradiance. The results clearly demonstrated that the PCI can enhance the delivery of both the PTEN or CD genes in human glioma cell monolayers and multicell tumor spheroids. The transfection efficiency, as measured by cell survival and inhibition of spheroid growth, was found to be significantly greater at suboptimal light and DNA levels for shelled NPs compared with polyamine-DNA polyplexes alone. (C) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE)
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