Abstract
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 (λ = 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.
Highlights
Photodynamic therapy (PDT) is an alternative cancer treatment modality in which a photosensitizing drug is administered to patients and a light of a specific wavelength is shed to them to kill their tumor cells via the production of reactive oxygen species (ROS) [1]
Superoxide released from KR-E. coli upon irradiation
This observation led us to the question whether ROS created by KillerRed inside the bacterial body could reach the tumor cells to provoke the phototoxicity
Summary
Photodynamic therapy (PDT) is an alternative cancer treatment modality in which a photosensitizing drug is administered to patients and a light of a specific wavelength is shed to them to kill their tumor cells via the production of reactive oxygen species (ROS) [1]. As a precursor of photosensitive protoporphyrin 9, 5-aminolevulinic acid (5-ALA) is commonly use These chemical compounds have several limitations including poor reproducibility, limited pharmacokinetics, impurity, and aggregation [5]. Administered photosensitizers preferentially accumulate in tumors compared with normal tissue Their selectivity may not be sufficiently high; treated patients often suffer from long-term skin sensitivities caused by the retention of photosensitizers in their skin and subsequent exposure to light [6]. This limitation has prompted the search for a new type of photosensitizer
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