Modulation of Hypoxia in Solid Tumor Microenvironment with MnO2 Nanoparticles to Enhance Photodynamic Therapy
Modulation of Hypoxia in Solid Tumor Microenvironment with MnO2 Nanoparticles to Enhance Photodynamic Therapy
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DOI：
10.1002/adfm.201600676
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发表时间：
2016-08-09
影响因子：
19
通讯作者：
Liu, Zhuang
中科院分区：
文献类型：
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作者：
Zhu, Wenwen;Dong, Ziliang;Liu, Zhuang
缺氧不仅促进肿瘤转移，而且增强肿瘤对需要氧气参与的治疗的抵抗，如放射治疗和光动力治疗（PDT）。本文利用二氧化锰（MnO2）纳米颗粒在肿瘤微环境中对内源性过氧化氢（H2O2）产生O-2的高反应性，制备了表面聚乙二醇（PEG）修饰的多功能氯e6 （Ce6）负载MnO2纳米颗粒（Ce6@MnO2-PEG），以实现增强的肿瘤特异性PDT。在缺氧环境下的体外研究发现，Ce6@MnO2-PEG纳米颗粒可以有效增强光诱导PDT的效果，这是由于MnO2与H2O2的反应增加了细胞内O-2水平，而H2O2是癌细胞在缺氧条件下产生的。t1加权磁共振成像显示，由于Ce6@MnO2-PEG纳米颗粒在静脉注射后能有效地定位肿瘤，在很大程度上缓解了肿瘤内缺氧。因此，与游离Ce6相比，含有Ce6@MnO2-PEG纳米颗粒的体内PDT即使在很大程度上降低了剂量，也能显著提高抑制肿瘤生长的治疗效果。这些结果强调了利用纳米技术调节不利的肿瘤微环境以克服当前癌症治疗的局限性的前景。
Hypoxia not only promotes tumor metastasis but also strengthens tumor resistance to therapies that demand the involvement of oxygen, such as radiation therapy and photodynamic therapy (PDT). Herein, taking advantage of the high reactivity of manganese dioxide (MnO2) nanoparticles toward endogenous hydrogen peroxide (H2O2) within the tumor microenvironment to generate O-2, multifunctional chlorine e6 (Ce6) loaded MnO2 nanoparticles with surface polyethylene glycol (PEG) modification (Ce6@MnO2-PEG) are formulated to achieve enhanced tumor-specific PDT. In vitro studies under an oxygen-deficient atmosphere uncover that Ce6@MnO2-PEG nanoparticles could effectively enhance the efficacy of light-induced PDT due to the increased intracellular O-2 level benefited from the reaction between MnO2 and H2O2, the latter of which is produced by cancer cells under the hypoxic condition. Owing to the efficient tumor homing of Ce6@MnO2-PEG nanoparticles upon intravenous injection as revealed by T1-weighted magnetic resonance imaging, the intratumoral hypoxia is alleviated to a great extent. Thus, in vivo PDT with Ce6@MnO2-PEG nanoparticles even at a largely reduced dose offers remarkably improved therapeutic efficacy in inhibiting tumor growth compared to free Ce6. The results highlight the promise of modulating unfavorable tumor microenvironment with nanotechnology to overcome current limitations of cancer therapies.