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Evaluation of mTHPC-loaded PLGA nanoparticles for in vitro photodynamic therapy on C6 glioma cell line

机译:载有mTHPC的PLGA纳米颗粒对C6胶质瘤细胞系进行体外光动力治疗的评估

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摘要

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 photo-sensitizers (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 (R)) 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 subset of 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 subset of 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 subset of 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 subset of PLGA NPs incubation and irradiation, annexin V staining tests were performed. The results indicated that apoptosis was the main cell death mechanism.
机译: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,例如放射疗法,外科手术和化学疗法。一些分子已显示出其作为光敏剂(PS)的效率,但仍需解决许多问题,例如PS固有的细胞毒性或疏水性会导致其溶解度受到限制,从而导致副作用。在这项研究中,通过纳米沉淀法在生物相容且可生物降解的聚(D,L-丙交酯-乙交酯)酸(PLGA)NPs中包封了批准的PS,内消旋四羟基苯氯(mTHPC,Foscan(R))被研究了。通过紫外-可见光谱分析了mTHPC负载的NPs(PLGA NPs的mTHPC子集),以确定mTHPC封装的效率,并通过动态光散射(DLS)和原子力显微镜(AFM)确定PLGA NPs大小的mTHPC子集,形态和表面电荷。从NPs释放mTHPC的纵向跟踪结果表明,经过5天的时间,50%的包封PS被保留在NP基质中。最后,在鼠C6神经胶质瘤细胞系中确定了PLGA NP的mTHPC亚型的细胞毒性和光毒性,并与单独的mTHPC进行了比较。研究表明,封装mTHPC后,mTHPC的细胞毒性大大降低,而mTHPC的光细胞毒性增加。为了更好地了解控制PLGA NPs的mTHPC亚型后细胞死亡的潜在细胞机制,进行了膜联蛋白V染色测试。结果表明凋亡是细胞死亡的主要机制。

著录项

  • 来源
    《Photodiagnosis and Photodynamic Therapy》 |2019年第3期|448-455|共8页
  • 作者单位

    Univ Reims, CNRS UMR 7312, Inst Chim Mol Reims, F-51687 Reims 2, France|Univ Reims, LRN, EA 4682, F-51685 Reims 2, France;

    Univ Reims, CNRS UMR 7312, Inst Chim Mol Reims, F-51687 Reims 2, France;

    Univ Reims, CNRS UMR 7312, Inst Chim Mol Reims, F-51687 Reims 2, France;

    Univ Reims, LRN, EA 4682, F-51685 Reims 2, France;

    Univ Reims, Fac Pharm, BioSpecT, F-51100 Reims, France;

    Univ Reims, CNRS UMR 7312, Inst Chim Mol Reims, F-51687 Reims 2, France|Univ Montreal, Fac Pharm, Lab Nanotechnol Pharmaceut, Montreal, PQ H3T 1J4, Canada;

    Univ Reims, PICT Platform, F-51100 Reims, France;

    Univ Reims, CNRS UMR 7312, Inst Chim Mol Reims, F-51687 Reims 2, France;

    Univ Reims, CNRS UMR 7312, Inst Chim Mol Reims, F-51687 Reims 2, France;

    Univ Reims, Fac Pharm, BioSpecT, F-51100 Reims, France;

    Univ Reims, LRN, EA 4682, F-51685 Reims 2, France|Univ Bordeaux, INP Bordeaux, CBMN CNRS UMR 5248, F-33600 Pessac, France;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Photodynamic therapy; PLGA nanoparticles; mTHPC encapsulation; Apoptosis; Cell death mechanism;

    机译:光动力疗法PLGA纳米粒mTHPC封装凋亡细胞死亡机制;

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