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载于可生物降解微乳液模板纳米胶囊中的疏水性花菁染料诱导 MCF-7 癌细胞的光氧化作用。

Photo-oxidative action in MCF-7 cancer cells induced by hydrophobic cyanines loaded in biodegradable microemulsion-templated nanocapsules.

机构信息

Department of Chemistry, Wroclaw University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wroclaw, Poland.

出版信息

Int J Oncol. 2012 Jul;41(1):105-16. doi: 10.3892/ijo.2012.1458. Epub 2012 May 2.

Abstract

Searching for photodynamic therapy-effective nanocarriers which enable a photosensitizer to be selectively delivered to tumor cells with enhanced bioavailability and diminished dark cytotoxicity is of current interest. We have employed a polymer-based nanoparticle approach to encapsulate the cyanine-type photosensitizer IR-780 in poly(n-butyl cyanoacrylate) (PBCA) nanocapsules. The latter were fabricated by interfacial polymerization in oil-in-water (o/w) microemulsions formed by dicephalic and gemini saccharide-derived surfactants. Nanocarriers were characterized by SEM, AFM and DLS. The efficiency of PBCA nanocapsules as a potential system of photosensitizer delivery to human breast cancer cells was established by dark and photocytotoxicity as the function of the cellular mitochondria. The photodynamic effect of cyanine IR-780 was determined by investigation of oxidative stress markers. The nanocapsules were the main focus of our studies to examine their cellular uptake and dark and photocytotoxicity as the function of the cellular mitochondria as well as oxidative stress markers (i.e., lipid peroxidation and protein damage) in MCF-7/WT cancer cells. The effects of encapsulated IR-780 were compared with those of native photosensitizer. The penetration of the nanocapsules into cancer cells was visualized by CLSM and their uptake was estimated by FACS analysis. Cyanine IR-780 delivered in PBCA nanocapsules to MCF-7/WT cells retains its sensitivity upon photoirradiation and it is regularly distributed in the cell cytoplasm. The intensity of the photosensitizer-generated oxidative stress depends on IR-780 release from the effective uptake of polymeric nanocapsules and seems to remain dependent upon the surfactant structure in o/w microemulsion-based templates applied to nanocapsule fabrication.

摘要

寻找光动力治疗有效的纳米载体,使光敏剂能够选择性地递送到肿瘤细胞,提高生物利用度,降低暗毒性,这是当前的研究热点。我们采用基于聚合物的纳米颗粒方法将花菁型光敏剂 IR-780 包封在聚 n-丁基氰基丙烯酸酯(PBCA)纳米胶囊中。后者通过在由双头和双子糖衍生的表面活性剂形成的油包水(o/w)微乳液中的界面聚合制备。通过 SEM、AFM 和 DLS 对纳米载体进行了表征。通过黑暗和光细胞毒性作为细胞线粒体的函数,确定了 PBCA 纳米胶囊作为潜在光敏剂递送到人乳腺癌细胞的系统的效率。通过研究氧化应激标志物来确定花菁 IR-780 的光动力效应。纳米胶囊是我们研究的重点,以研究它们的细胞摄取、黑暗和光细胞毒性作为细胞线粒体以及氧化应激标志物(即脂质过氧化和蛋白质损伤)的功能在 MCF-7/WT 癌细胞中。与天然光敏剂相比,研究了包裹的 IR-780 的效果。通过 CLSM 可视化纳米胶囊进入癌细胞的穿透情况,并通过 FACS 分析估计其摄取量。递送到 MCF-7/WT 细胞的 PBCA 纳米胶囊中的花菁 IR-780 在光照射下保持其敏感性,并且在细胞质中均匀分布。光敏剂产生的氧化应激的强度取决于从有效摄取聚合物纳米胶囊释放的 IR-780,并且似乎仍然依赖于应用于纳米胶囊制造的 o/w 微乳液模板中的表面活性剂结构。

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