Barras Alexandre, Skandrani Nadia, Gonzalez Pisfil Mariano, Paryzhak Solomiya, Dumych Tetiana, Haustrate Aurélien, Héliot Laurent, Gharbi Tijani, Boulahdour Hatem, Lehen'kyi V'yacheslav, Bilyy Rostyslav, Szunerits Sabine, Bidaux Gabriel, Boukherroub Rabah
Univ. Lille, CNRS, Centrale Lille, ISEN, Univ. Valenciennes, UMR 8520 - IEMN, F-59000 Lille, France.
J Mater Chem B. 2018 Oct 7;6(37):5949-5963. doi: 10.1039/c8tb01759j. Epub 2018 Sep 6.
Photodynamic therapy (PDT) has developed into a new clinical and non-invasive treatment for cancer over the past 30 years. By the combination of three non-toxic partners, i.e. a photosensitizer (PS), molecular oxygen (O) and light, cytotoxic reactive oxygen species (ROS) are locally produced leading to irreversible vascular and cellular damage. In the present study, we report for the first time that the combination of two photosensitizers (2 PSs: Protoporphyrin IX, PpIX and Hypericin, Hy) loaded in the same lipid nanocapsules (LNCs) leads to enhanced photodynamic therapy efficiency when compared with previously reported systems. The 2 PS-loaded LNCs are shown to increase the in vitro phototoxicity at the nanomolar range (IC = 274 and 278 nM on HeLa and MDA-MB-231 cell lines, respectively), whereas the corresponding single PS-loaded LNCs at the same concentration exhibit a phototoxicity two times lower. Intracellular localization in HeLa cells indicates a subcellular asymmetry of PpIX and Hy, in the plasma, ER membranes and round internal structures. The biodistribution of LNCs was studied upon different routes of injection into Swiss nude mice; based on the obtained data, LNCs were injected intratumorally and used to slow the growth of xenograft tumors in mice. The results obtained in this study suggest that the combination of two or more PSs may be a promising strategy to improve the efficacy of conventional photodynamic therapy as well as to reduce dark toxicity.
在过去30年里，光动力疗法（PDT）已发展成为一种新型的癌症临床无创治疗方法。通过三种无毒成分的组合，即光敏剂（PS）、分子氧（O）和光，可在局部产生细胞毒性活性氧（ROS），从而导致不可逆的血管和细胞损伤。在本研究中，我们首次报告，与先前报道的系统相比，负载在同一脂质纳米囊（LNC）中的两种光敏剂（两种PS：原卟啉IX，PpIX和金丝桃素，Hy）的组合可提高光动力治疗效率。负载两种PS 的LNC在纳摩尔范围内可提高体外光毒性（对HeLa和MDA-MB-231细胞系的IC50分别为274和278 nM），而相同浓度下相应的负载单一PS的LNC的光毒性则低两倍。在HeLa细胞中的细胞内定位表明，PpIX和Hy在细胞质、内质网膜和圆形内部结构中存在亚细胞不对称性。在将LNC通过不同注射途径注入瑞士裸鼠后研究了其生物分布；基于获得的数据，将LNC瘤内注射并用于减缓小鼠异种移植肿瘤的生长。本研究获得的结果表明，两种或更多种PS的组合可能是一种有前景的策略，可提高传统光动力疗法的疗效并降低暗毒性。
