Thandu Merlyn, Rapozzi Valentina, Xodo Luigi, Albericio Fernando, Comuzzi Clara, Cavalli Silvia
Department of Chemistry, Physics and Environment, University of Udine, Via del Cotonificio 108, 33100 Udine (Italy).
Department of Medical and Biological Sciences, School of Medicine, University of Udine, Piazzale Kolbe 4, 33100 Udine (Italy).
Chempluschem. 2014 Jan;79(1):90-98. doi: 10.1002/cplu.201300276. Epub 2013 Oct 23.
A method for the preparation of superparamagnetic iron oxide nanoparticle-porphyrin (SPION-TPP) conjugates through click chemistry, which can be used as novel theranostic nanoagents for photodynamic therapy is developed. The synthesis, characterisation, and evaluation of the photocytotoxicity profiles of the nanoconjugates prepared is reported. Upon light irradiation, SPION-TPP nanoconstructs promote a photodynamic effect in vitro in murine amelanotic melanoma B78-H1 cells, with IC values in the region of 800 nM, similarly to unbound TPP, whereas they remain non-cytotoxic in the dark. However, these nanoconstructs show poor cellular uptake, which influences a linear dose-response effect. Therefore, the improvement of delivery to cells has also been studied by conjugating a well-known cell-penetrating peptide (TAT peptide) to the SPION-TPP nanoparticles. The new nanoconstructs show lower IC values (in the region of 500 nM) and a clear dose-response effect. Our results suggest that TAT-conjugated SPION-TPP nanoparticles are efficient nanodevices both for tracking drugs by means of magnetic resonance imaging (MRI)-based techniques and for treating cancer cells through photodynamic therapy, thus functioning as promising theranostic nanoagents.
开发了一种通过点击化学制备超顺磁性氧化铁纳米颗粒-卟啉（SPION-TPP）共轭物的方法，该共轭物可用作光动力疗法的新型诊疗纳米剂。报道了所制备的纳米共轭物的合成、表征及其光细胞毒性谱的评估。光照后，SPION-TPP纳米结构在体外对小鼠无黑色素黑色素瘤B78-H1细胞产生光动力效应，IC值在800 nM左右，与未结合的TPP相似，而在黑暗中它们仍无细胞毒性。然而，这些纳米结构的细胞摄取较差，这影响了线性剂量反应效应。因此，还通过将一种著名的细胞穿透肽（TAT肽）与SPION-TPP纳米颗粒偶联来研究细胞递送的改善。新的纳米结构显示出较低的IC值（在500 nM左右）和明显的剂量反应效应。我们的结果表明，TAT偶联的SPION-TPP纳米颗粒是高效的纳米器件，既可以通过基于磁共振成像（MRI）的技术追踪药物，又可以通过光动力疗法治疗癌细胞，因此是有前景的诊疗纳米剂。
