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2015 ; 10
(7
): e0131518
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Photodynamic Treatment of Tumor with Bacteria Expressing KillerRed
#MMPMID26213989
Yan L
; Kanada M
; Zhang J
; Okazaki S
; Terakawa S
PLoS One
2015[]; 10
(7
): e0131518
PMID26213989
show ga
Photodynamic therapy (PDT) is a cancer treatment modality in which a
photosensitizing dye is administered and exposed to light to kill tumor cells via
the production of reactive oxygen species (ROS). A fundamental obstacle for PDT
is the low specificity for staining solid tumors with dyes. Recently, a tumor
targeting system guided by anaerobic bacteria was proposed for tumor imaging and
treatment. Here, we explore the feasibility of the genetically encoded
photosensitizer KillerRed, which is expressed in Escherichia coli, to treat
tumors. Using nitroblue tetrazolium (NBT), we detected a lengthy ROS diffusion
from the bodies of KillerRed-expressing bacteria in vitro, which demonstrated the
feasibility of using bacteria to eradicate cells in their surroundings. In nude
mice, Escherichia coli (E. coli) expressing KillerRed (KR-E. coli) were
subcutaneously injected into xenografts comprising CNE2 cells, a human
nasopharyngeal carcinoma cell line, and HeLa cells, a human cervical carcinoma
cell line. KR-E. coli seemed to proliferate rapidly in the tumors as observed
under an imaging system. When the intensity of fluorescence increased and the
fluorescent area became as large as the tumor one day after KR-E. coli injection,
the KR-E. coli-bearing tumor was irradiated with an orange light (? = 540-580
nm). In all cases, the tumors became necrotic the next day and were completely
eliminated in a few days. No necrosis was observed after the irradiation of
tumors injected with a vehicle solution or a vehicle carrying the E. coli without
KillerRed. In successfully treated mice, no tumor recurrence was observed for
more than two months. E. coli genetically engineered for KillerRed expression are
highly promising for the diagnosis and treatment of tumors when the use of
bacteria in patients is cleared for infection safety.