锰氧化物和高度还原氧化石墨烯的杂化纳米粒子用于光动力疗法。

Hybrid Nanoparticles of Manganese Oxide and Highly Reduced Graphene Oxide for Photodynamic Therapy.

机构信息

Department of Biochemistry, College of Science, King Saud University, 11451 Riyadh, Saudi Arabia.

Department of Chemical and Biological Engineering, Korea National University of Transportation, 27469 Chungju, Republic of Korea.

出版信息

Front Biosci (Landmark Ed). 2023 Jan 18;28(1):19. doi: 10.31083/j.fbl2801019.

DOI:10.31083/j.fbl2801019

PMID:36722275

Abstract

BACKGROUND

Graphene-based nanomaterials possess unique optical, physicochemical and biomedical properties which make them potential tools for imaging and therapy. Manganese oxide nanoparticles are attractive candidates for contrast agents in magnetic resonance imagint (MRI). We used manganese oxide (Mn3O4) and highly reduced graphene oxide (HRG) to synthesize hybrid nanoparticles (HRG-Mn3O4) and tested their efficacy for photodynamic therapy (PDT) in breast cancer cells.

METHODS

The newly synthesized nanoparticles were characterized by transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) spectroscopy, UV-visible spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetry, and X-ray diffraction (XRD) analyses. We used standard protocols of cytotoxicity and PDT after exposing A549 cells to various concentrations of hybrid nanoparticles (HRG-Mn3O4). We also performed fluorescence microscopy for live/dead cellular analysis. A549 cells were incubated with nanoparticles for 24 h and stained with fluorescein diacetate (green emission for live cells) and propidium iodide (red emission for dead cells) to visualize live and dead cells, respectively.

RESULTS

The cell viability analysis showed that more than 98% of A549 cells survived even after the exposure of a high concentration (100 μg/mL) of nanomaterials. These results confirmed that the HRG-Mn3O4 nanoparticles are nontoxic and biocompatible at physiological conditions. When the cell viability analysis was performed after laser irradiation, we observed significant and concentration-dependent cytotoxicity of HRG-Mn3O4 as compared to Mn3O4 nanoparticles. Fluorescence microscopy showed that almost 100% cells were viable when treated with phosphate buffered saline or Mn3O4 while only few dead cells were detected after exposure of HRG-Mn3O4 nanoparticles. However, laser irradiation resulted in massive cellular damage by HRG-Mn3O4 nanoparticles which was directly related to the generation of reactive oxygen species (ROS).

CONCLUSIONS

HRG-Mn3O4 hybrid nanoparticles are stable, biocompatible, nontoxic, and possess therapeutic potential for photodynamic therapy of cancer. Further studies are warranted to explore the MRI imaging ability of these nanomaterials using animal models of cancer.

摘要

背景

基于石墨烯的纳米材料具有独特的光学、物理化学和生物医学特性，使其成为成像和治疗的潜在工具。氧化锰纳米粒子是磁共振成像（MRI）中造影剂的有吸引力的候选物。我们使用氧化锰（Mn3O4）和高度还原的氧化石墨烯（HRG）合成了混合纳米粒子（HRG-Mn3O4），并测试了它们在乳腺癌细胞中的光动力治疗（PDT）效果。

方法

新合成的纳米粒子通过透射电子显微镜（TEM）、能量色散 X 射线（EDX）光谱、紫外可见光谱、傅里叶变换红外（FT-IR）光谱、热重分析和 X 射线衍射（XRD）分析进行了表征。我们使用 A549 细胞暴露于不同浓度的混合纳米粒子（HRG-Mn3O4）后的细胞毒性和 PDT 的标准方案。我们还进行了荧光显微镜活/死细胞分析。将 A549 细胞与纳米粒子孵育 24 小时，并用荧光素二乙酸（活细胞的绿色发射）和碘化丙啶（死细胞的红色发射）染色，分别可视化活细胞和死细胞。

结果

细胞活力分析表明，即使在暴露于高浓度（100μg/mL）纳米材料后，超过 98%的 A549 细胞仍然存活。这些结果证实，HRG-Mn3O4 纳米粒子在生理条件下是无毒和生物相容的。当进行激光照射后的细胞活力分析时，与 Mn3O4 纳米粒子相比，我们观察到 HRG-Mn3O4 的显著且浓度依赖性细胞毒性。荧光显微镜显示，用磷酸盐缓冲盐水或 Mn3O4 处理时，几乎 100%的细胞存活，而暴露于 HRG-Mn3O4 纳米粒子后仅检测到少数死细胞。然而，激光照射导致 HRG-Mn3O4 纳米粒子引起大量细胞损伤，这与活性氧（ROS）的产生直接相关。