Nafiujjaman Md, Chung Seock-Jin, Kalashnikova Irina, Hill Meghan L, Homa Silver, George Jeron, Contag Christopher H, Kim Taeho
Department of Biomedical Engineering, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, Michigan 48824, United States.
Department of Biological, Physical, and Health Sciences, Roosevelt University, Chicago, Illinois 60605, United States.
ACS Appl Bio Mater. 2020 Nov 16;3(11):7989-7999. doi: 10.1021/acsabm.0c01079. Epub 2020 Oct 27.
Photodynamic therapy (PDT) has been extensively explored as a minimally invasive treatment strategy for malignant cancers. It works with the help of a photosensitizer located within cancer cells that is irradiated by near-infrared light to produce potent toxins and singlet oxygen (O) and induce cell death. However, reactive oxygen species can be overexpressed in tumor tissue because of the rapid metabolic activity in cancer cells, and the insufficient oxygenation (hypoxia) can lead to low production of singlet oxygen (O) during PDT. In this study, we developed nanocomposites composed of a hollow manganese silicate (HMnOSi) nanoparticle and a photosensitizer (Ce6) that can generate significant amounts of O to relieve tumor hypoxia and enhance the therapeutic efficacy of PDT. Our nanocomposites were characterized by UV-vis, fluorescence spectroscopy, transmission electron microscopy (TEM), energy-dispersive X-ray, and dynamic light scattering. Our particles' hollow mesoporous structures were shown to retain large amounts of Ce6 on the particle surface with high loading capacity (33%). TEM imaging showed that the nanoparticles could be biodegradable over time in simulated body fluid, which can imply clinical potentials. Significant HO quenching capabilities to alleviate hypoxic conditions in a solid tumor were also presented. For breast cancer cells, the nanocomposite-treated group revealed that 91% of cells were dead under laser activation compared to 51% for the control group (free Ce6). In an animal study, our nanocomposites showed almost fourfold tumor growth inhibition versus the control and more than twofold over free Ce6 in orthotopic tumor xenografts. In addition, the oxygen saturation contrast inside tumors was evaluated by photoacoustic imaging to demonstrate the alleviated hypoxia in vivo. Our works provide a smart nanosystem to ameliorate the hypoxic tumor microenvironment and augment the efficacy of PDT in a targeted cancer treatment.
光动力疗法（PDT）作为一种针对恶性肿瘤的微创治疗策略已得到广泛研究。它借助位于癌细胞内的光敏剂发挥作用，该光敏剂在近红外光照射下产生强效毒素和单线态氧（O），从而诱导细胞死亡。然而，由于癌细胞快速的代谢活性，活性氧在肿瘤组织中可能会过度表达，并且氧合不足（缺氧）会导致光动力疗法期间单线态氧（O）产生量较低。在本研究中，我们开发了由中空硅酸锰（HMnOSi）纳米颗粒和光敏剂（Ce6）组成的纳米复合材料，该复合材料可产生大量的O以缓解肿瘤缺氧并增强光动力疗法的治疗效果。我们的纳米复合材料通过紫外可见光谱、荧光光谱、透射电子显微镜（TEM）、能量色散X射线和动态光散射进行表征。我们的颗粒的中空介孔结构显示出在颗粒表面保留大量Ce6且具有高负载能力（33%）。TEM成像表明，纳米颗粒在模拟体液中可随时间生物降解，这暗示了其临床潜力。还展示了该纳米复合材料具有显著的HO猝灭能力，可缓解实体瘤中的缺氧状况。对于乳腺癌细胞，纳米复合材料处理组显示在激光激活下91%的细胞死亡，而对照组（游离Ce6）为51%。在动物研究中，我们的纳米复合材料在原位肿瘤异种移植中显示出与对照组相比肿瘤生长抑制几乎提高了四倍，比游离Ce6高出两倍多。此外，通过光声成像评估肿瘤内部的氧饱和度对比度，以证明体内缺氧状况得到缓解。我们的工作提供了一种智能纳米系统，可改善缺氧肿瘤微环境并增强光动力疗法在靶向癌症治疗中的疗效。
