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Glioma cell growth inhibition following photochemical internalization enhanced non‐viral PTEN gene transfection
Author(s) -
Mathews Marlon S.,
Shih EnChung,
Zamora Genesis,
Sun ChungHo,
Cho Soo Kyung,
Kwon Young Jik,
Hirschberg Henry
Publication year - 2012
Publication title -
lasers in surgery and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 112
eISSN - 1096-9101
pISSN - 0196-8092
DOI - 10.1002/lsm.22082
Subject(s) - transfection , pten , gene delivery , green fluorescent protein , glioma , microbiology and biotechnology , genetic enhancement , chemistry , lipofectamine , cancer research , biology , gene , biochemistry , pi3k/akt/mtor pathway , signal transduction , vector (molecular biology) , recombinant dna
Background and Objective One of many limitations for cancer gene therapy is the inability of the therapeutic gene to transfect a sufficient number of tumor cells. Photochemical internalization (PCI) is a photodynamic therapy‐based approach for improving the delivery of macromolecules and genes into the cell cytosol. The utility of PCI for the delivery of the GFP reporter gene on the same plasmid as a tumor suppressor gene (PTEN) was investigated in monolayers of U251 human glioma cells and muticell U87 glioma spheroids. Materials and Methods U251 monolayers or U87 spheroids were incubated in AlPcS 2a and non‐viral vector polyplexes for 18 hours. In all cases, light treatment was performed with a diode laser at a wavelength of 670 nm. The non‐viral transfection agents, branched polyethylenimine (bPEI), or protamine sulfate (PS), were used with the plasmid constructs GFP/PTEN or GFP. Results PS/GFP polyplexes were much less toxic to the glioma cells compared to bPEI/GFP polyplexes but were highly inefficient at gene transfection if used alone. PCI resulted in a 5‐ to 10‐fold increase in GFP protein expression compared to controls. PCI‐bPEI/PTEN or PCI‐PS/PTEN transfection of either U251 monolayers or U87 spheroids significantly inhibited their growth. but had no effect on MCF‐7 cells containing a wild‐type PTEN gene. In addition PCI‐GFP transfection of gliomas cells had no effect on their growth pattern. Conclusions Collectively, the results suggest that AlPcS 2a ‐mediated PCI can be used to enhance cell growth inhibition via transfection of tumor suppressor genes in glioma cells containing mutant PTEN genes. Lasers Surg. Med. 44: 746–754, 2012. © 2012 Wiley Periodicals, Inc.