评价载 mTHPC 的 PLGA 纳米粒用于 C6 神经胶质瘤细胞系的体外光动力治疗。
Evaluation of mTHPC-loaded PLGA nanoparticles for in vitro photodynamic therapy on C6 glioma cell line.
机构信息
Institut de Chimie Moléculaire de Reims, CNRS UMR 7312, University of Reims Champagne Ardenne, 51687, Reims Cedex 2, France; Laboratoire de Recherche en Nanosciences LRN EA 4682, University of Reims Champagne-Ardenne URCA, 51685, Reims Cedex 2, France.
Institut de Chimie Moléculaire de Reims, CNRS UMR 7312, University of Reims Champagne Ardenne, 51687, Reims Cedex 2, France.
出版信息
Photodiagnosis Photodyn Ther. 2019 Mar;25:448-455. doi: 10.1016/j.pdpdt.2019.01.026. Epub 2019 Jan 29.
Photodynamic therapy (PDT) is a very attractive strategy to complement or replace common cancer treatments such as radiotherapy, surgery, and chemotherapy. Some molecules have shown their efficiency as photosensitizers (PS), still many issues have to be solved such as the inherent cytotoxicity of the PS or its hydrophobic properties causing limitation in their solubility, leading to side effects. In this study, the encapsulation of an approved PS, the meso-tetra hydroxyphenylchlorine (mTHPC, Foscan®) within biocompatible and biodegradable poly(D, l-lactide-co-glycolide) acid (PLGA) NPs prepared by the nanoprecipitation method was studied. The mTHPC-loaded NPs (mTHPC ⊂ PLGA NPs) were analyzed by UV-vis spectroscopy to determine the efficiency of mTHPC encapsulation, and by dynamic light scattering (DLS) and atomic force microscopy (AFM) to determine mTHPC ⊂ PLGA NPs sizes, morphologies and surface charges. The longitudinal follow-up of mTHPC release from the NPs indicated that 50% of the encapsulated PS was retained within the NP matrix after a period of five days. Finally, the cytotoxicity and the phototoxicity of the mTHPC ⊂ PLGA NPs were determined in murine C6 glioma cell lines and compared to the ones of mTHPC alone. The studies showed a strong decrease of mTHPC cytotoxicity and an increase of mTHPC photo-cytotoxicity when mTHPC was encapsulated. In order to have a better insight of the underlying cellular mechanisms that governed cell death after mTHPC ⊂ PLGA NPs incubation and irradiation, annexin V staining tests were performed. The results indicated that apoptosis was the main cell death mechanism.
光动力疗法（PDT）是一种非常有吸引力的策略，可以补充或替代常见的癌症治疗方法，如放疗、手术和化疗。一些分子已被证明具有作为光敏剂（PS）的功效，但仍有许多问题需要解决，例如 PS 的固有细胞毒性或其疏水性导致其在溶解度方面的限制，从而导致副作用。在这项研究中，研究了将一种已批准的 PS（meso-四羟基苯基氯（mTHPC，Foscan®））封装在生物相容性和可生物降解的聚（D，L-丙交酯-co-乙交酯）酸（PLGA）纳米粒子内通过纳米沉淀法制备。通过紫外可见分光光度法分析载 mTHPC 的 NPs（mTHPC⊂PLGA NPs）以确定 mTHPC 包封效率，并通过动态光散射（DLS）和原子力显微镜（AFM）确定 mTHPC⊂PLGA NPs 的尺寸、形态和表面电荷。mTHPC 从 NPs 中的纵向释放跟踪表明，在五天的时间内，50%的封装 PS 保留在 NP 基质中。最后，在小鼠 C6 神经胶质瘤细胞系中测定了 mTHPC⊂PLGA NPs 的细胞毒性和光毒性，并与单独的 mTHPC 进行了比较。研究表明，当 mTHPC 被封装时，mTHPC 的细胞毒性大大降低，而 mTHPC 的光细胞毒性增加。为了更深入地了解 mTHPC⊂PLGA NPs 孵育和照射后导致细胞死亡的潜在细胞机制，进行了 Annexin V 染色试验。结果表明，细胞凋亡是主要的细胞死亡机制。
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