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  • br Keywords br Chemodynamic therapy br

    2019-10-30

    Keywords:
    Chemodynamic therapy
    Limotherapy
    Magnetic resonance imaging
    Nanoselenium
    Superoxide dismutase 
    Chemodynamic therapy (CDT) was widely exploited for cancer therapy and expected to replace traditional anticancer drug therapies. Generally, CDT needs to combine with extra therapeutic methods for obtaining the optimal therapeutic efficacy of cancer. Herein, a multifunctional theranostic platform combing CDT with li-motherapy was developed via nanoselenium (nano-Se)-coated manganese carbonate-deposited iron oxide na-noparticle (MCDION-Se). MCDION-Se could release abundant of Mn2+ ions that catalyzed H2O2 into hydroxyl radicals (·OH) via a Fenton-like reaction, effectively inducing the apoptosis of cancer cells. Besides, nano-Se coated onto MCDION-Se also dramatically activated super oxide dismutase (SOD) and promoted the generation of superoxide anion radicals (SOARs) in tumor tissue. Subsequently, a high content of H2O2 was produced via SOD catalysis of SOARs, further enhancing CDT efficiency. Meanwhile, the nano-Se and Mn2+ ions inhibited the generation of adenosine triphosphate (ATP), thus starving cancer cells. In addition, in vitro and in vivo ex-periments showed that MCDION-Se could effectively enhance the CCK8 of tumor tissue and improve the quality of magnetic resonance imaging (MRI). Overall, this work provided a nanoplatform that combined CDT with limotherapy for cancer therapy and simultaneously utilized MRI for monitoring the treatment of tumors.
    1. Introduction
    In recent decades, the development of new chemotherapeutic has rapidly progressed because of the sharp increase in the number of cancer patients [1]. Currently, clinical chemotherapeutics mainly in-clude docetaxel [2], doxorubicin [3,4], cisplatin [5], and hydro-xycamptothecin and so on [6,7]. Nevertheless, these drugs were sig-nificantly limited in clinical use because of high prices and serious side effects [8,9]. Therefore, the development of drug-free therapeutic agents to decrease the cost of cancer treatment and reduce the side effects of traditional chemotherapeutics has received increased atten-tion.
    * Corresponding author.
    ** Corresponding author.
    Recently, chemodynamic therapy (CDT) was widely explored for its potential to replace traditional chemotherapeutics because excessive hydroxyl radicals (·OH) can cause DNA and proteins damage and ac-celerate cancer cell apoptosis [10–13]. As previously reported [14–17], the microenvironment of tumor tissue was beneficial for the generation of toxic ·OH under CDT agent stimulus, which could effectively induce cancer cell apoptosis. Generally, the body had the natural CDT agent (i.e. Fe ion) which catalyzed H2O2 into ·OH via the Fenton reaction [18,19]. Nevertheless, the content of Fe ions in cancer cells is too low, which decreased the efficiency of Fenton reaction, so that the content of ·OH generated by Fe ion catalysis is insufficient to cause cancer cell apoptosis. Therefore, the supplement of extra CDT agent was important
    to enhance catalytic efficiency of Fenton reaction and accelerate the generation of toxic ·OH. However, restricted by the concentration of H2O2, simple CDT was difficult to obtain a significant advantage for cancer therapy in comparison with traditional chemotherapeutics [20]. To solve this problem, the CDT nanoplatform usually needs to combine with other therapeutic methods to achieve the desired treatment effect.
    For instance, Lin et al. combined CDT with chemotherapy to en-hance the therapeutic efficacy of a iron-based nanoplatform against cancer [21]. Meng et al. developed a Mn-doped zirconium metal-or-ganic framework nanoplatform that combined CDT with microwave dynamic-thermal therapy for achieving synergistic cancer therapy [22]. In summary, these novel nanoplatforms showed a significantly better treatment effect on cancer than that of simple CDT agents. However, the integration of extra therapeutic methods needed some expensive equipments, which increased the complexity and cost of the cancer treatment and###http://www.glpbio.com/simage/GC13869-Fasudil-5.png#### limited their extensive application. Therefore, there is a challenge to construct a multifunctional drug-free CDT platform to optimize cancer treatment and decrease side effects in the body. No-tably, nanoselenium (nano-Se) could promote the generation of super-oxide anion radicals (SOARs) and also activate superoxide dismutase (SOD) in vivo [23–29]. Meanwhile, the SOARs would be further cata-lyzed by SOD and then generate H2O2, which could enhance the content of H2O2 in vivo. Therefore, nano-Se could be an excellent booster to enhance the hydroxyl radical level after the integration of the CDT agent.