Molinari A, Colone M, Calcabrini A, Stringaro A, Toccacieli L, Arancia G, Mannino S, Mangiola A, Maira G, Bombelli C, Mancini G
Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy.
Toxicol In Vitro. 2007 Mar;21(2):230-4. doi: 10.1016/j.tiv.2006.09.006. Epub 2006 Sep 19.
In this study we investigated the feasibility of mixed liposomes formed by dimyristoyl-sn-glycero-phosphatidylcholine (DMPC) and cationic gemini surfactant (Gemini 1) loaded with the chlorin m-tetrahydroxyphenylchlorin (m-THPC), in photodynamic therapy (PDT) for glioma. To this aim, an in vitro study was carried out by employing various human glioblastoma cell lines (A172, DBTRG, LN229, U118). The following liposomal formulations were tested: (i) DMPC and Gemini 1; (ii) m-THPC in DMPC in the absence or (iii) in the presence of Gemini 1 in the molar ratio 8:2; 7:3, and 6:4. The presence of Gemini 1 significantly increased the intracellular uptake of chlorin in all cell tested although with a different extent: LN229>U118>A172>DBTRG. The cytotoxicity of chlorin-loaded liposomes was then tested by cloning efficiency performed on different cultures, before and after irradiation with laser light at 652nm, at a Fluence Rate of 200mW/s for 100s, with a total Fluence of 20J/cm(-2). In the absence of irradiation, the different liposomal formulations induced a cytotoxicity in less than 30% of glioblastoma cells. On the contrary, irradiation induced total destruction of all cultures treated with m-THPC/DMPC+Gemini 1 in the ratios 8:2, or 7:3, or 6:4.
在本研究中,我们探究了由二肉豆蔻酰 - sn - 甘油 - 磷脂酰胆碱(DMPC)和阳离子双子表面活性剂(Gemini 1)形成的混合脂质体负载二氢卟吩 - m - 四羟基苯基二氢卟吩(m - THPC)用于胶质瘤光动力疗法(PDT)的可行性。为此,通过使用各种人胶质母细胞瘤细胞系(A172、DBTRG、LN229、U118)进行了一项体外研究。测试了以下脂质体制剂:(i)DMPC和Gemini 1;(ii)在不存在Gemini 1的情况下,m - THPC负载于DMPC中;(iii)在存在Gemini 1的情况下,二者摩尔比为8:2、7:3和6:4。Gemini 1的存在显著增加了所有测试细胞中二氢卟吩的细胞内摄取,尽管程度不同:LN229>U118>A172>DBTRG。然后,通过对不同培养物进行克隆效率测试来检测负载二氢卟吩的脂质体的细胞毒性,在652nm波长的激光照射前后进行测试,光通量率为200mW/s,照射100s,总光通量为20J/cm(-2)。在无照射的情况下,不同脂质体制剂在不到30%的胶质母细胞瘤细胞中诱导细胞毒性。相反,照射导致所有用摩尔比为8:2、7:3或6:4的m - THPC/DMPC + Gemini 1处理的培养物完全被破坏。