A Fluorescent Probe Used In Detection Of Tumor Marker And Targeted Photodynamic Therapy

Photosensitizer (PS) can be activated by a specific wavelength of light and generate singlet oxygen, causing selective damage to tissues in situ for photodynamic therapy (PDT). Many PSs are bright fluorophores, they tend to emit in the near-infrared (NIR) portion of the spectra. Fluorescent PS can determine PS localization and degree of PS uptake by diseased tissue, differentiate normal and malignant regions, use in vivo imaging acting as an image-guidance tool for cancer diagnosis. In addition, evaluation of PDT treatment may be monitored through the PS fluorescence.Nonspecific localization of imaging and therapeutic agents often leads to suboptimal treatment outcomes and unintended toxicity to normal tissues following exposure to light irradiation during PDT. Numerous attempts have been made to alter the structure of PS by moderating physiochemical properties such as hydrophilicity, hydrophobicity, charge, and delivery strategies to achieve optimum activity for photodynamic action, but even the high accumulation of PS at the target tissue in vitro does not warrant an ideal outcome in vivo. A number of target-specific strategies for PDT have been developed to avoid these problems and improve PS specificity for diseased tissue. Two key strategies to enhance PS selectivity: (1) the utilization of site-specific delivery agents such as nanoparticles, antibodies, aptamers and peptides that carry PSs to targeted tissue, (2) the synthesis of target-activated PDT agents that remain optically and photodynamically inactive until encountering the target (e.g., protease, nucleic acids, environment) for selective activation and retention at the site of interest.Tumor marker is over-expressed in tumor cells but not in normal cells, which may provide new avenues to monitor tumor progression and assess response to treatment. Targeted PDT in which tumor markers are targets can selectively kill tumor cells and rarely damage normal cells. Therefore, simultaneous detection of tumor markers and targeted therapy would be highly significant for cancer diagnosis and therapy.In this study, the recent research progress on detection of tumor markers and tumor selectivity of PS and their application in cancer diagnosis and therapy are reviewed. Based on the above, we developed a sensitive and effective survivin mRNA-mediated bi-photosensitizer molecular beacon (bi-PS MB) for detection of survivin mRNA and targeted therapy. Survivin mRNA is a tumor mRNA of breast cancer. The fluorescence and singlet oxygen generation occurred effectively in breast cancer cells, but not in normal cells. The fluorescence intensity and singlet oxygen generation were correlated well with the level of tumor mRNA expression in the cells. Significantly, bi-PS MB exhibited higher SB ratio and better PDT effect than single-PS MB.