title: Photochemical internalization-mediated nonviral gene transfection: polyamine core-shell nanoparticles as gene carrier.
abstract: 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 AlPcS 2a and λ=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.
authors.affiliation: University of California, Beckman Laser Institute, 1002 Health Sciences Road East, Irvine, California 92612, United States.
authors.forename: Genesis
authors.initials: G
authors.lastname: Zamora
authors.affiliation: University of California, Beckman Laser Institute, 1002 Health Sciences Road East, Irvine, California 92612, United States.
authors.forename: Frederick
authors.initials: F
authors.lastname: Wang
authors.affiliation: University of California, Beckman Laser Institute, 1002 Health Sciences Road East, Irvine, California 92612, United States.
authors.forename: Chung-Ho
authors.initials: CH
authors.lastname: Sun
authors.affiliation: University of California, Beckman Laser Institute, 1002 Health Sciences Road East, Irvine, California 92612, United States.
authors.forename: Anthony
authors.initials: A
authors.lastname: Trinidad
authors.affiliation: University of California, Department of Chemical Engineering/Material Science, 916 Engineering Tower, Irvine, California 92697-2575, United StatescUniversity of California, Department of Pharmaceutical Sciences, 147 Bison Modular, Irvine, California 92697.
authors.forename: Young Jik
authors.initials: YJ
authors.lastname: Kwon
authors.affiliation: University of California, Department of Chemical Engineering/Material Science, 916 Engineering Tower, Irvine, California 92697-2575, United States.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Cho
authors.affiliation: Oslo University Hospital, The Norwegian Radium Hospital, Department of Radiation Biology, Ullernchausseen 70, Oslo 0379, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Berg
authors.affiliation: University of Nevada, Department of Health Physics and Diagnostic Sciences, 4505 Maryland Parkway, Las Vegas, Nevada 89154, United States.
authors.forename: Steen J
authors.initials: SJ
authors.lastname: Madsen
authors.affiliation: University of California, Beckman Laser Institute, 1002 Health Sciences Road East, Irvine, California 92612, United StateseUniversity of Nevada, Department of Health Physics and Diagnostic Sciences, 4505 Maryland Parkway, Las Vegas, Nevada 89154, United S.
authors.forename: Henry
authors.initials: H
authors.lastname: Hirschberg
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D015316:Genetic Therapy; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D011073:Polyamines / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D018874:Spheroids, Cellular; D014162:Transfection / Q000379:methods*
chemical_list: D004337:Drug Carriers; D017319:Photosensitizing Agents; D011073:Polyamines; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D043525:Cytosine Deaminase