中文摘要:光动力疗法(PDT)是一种很有前途的癌症治疗方法。本文使用正交纳米结构方法(遗传/化学)设计M13噬菌体作为靶向载体,以高效光动力杀死癌细胞。M13经过基因重组,在噬菌体顶端显示一种能够结合表皮生长因子受体(EGFR)的肽(SYPIPDT)。重组的M13(EGFR)噬菌体表现出EGFR靶向性,并被过表达EGFR的A431癌细胞内化。采用正交方法对M13(EGFR)噬菌体进行化学修饰,不影响SYPIPDT肽选择性识别的前提下,在衣壳表面结合数百个孟加拉玫瑰(RB)光敏分子。内化后,M13(EGFR)-RB衍生物产生细胞内活性氧,被超低强度白光照射激活。在皮摩尔浓度下M13(EGFR)噬菌体对癌细胞具有杀伤活性。
外文摘要:Photodynamic therapy (PDT) represents a promising therapeutic modality for cancer. Here we used an orthogonal nanoarchitectonics approach (genetic/chemical) to engineer M13 bacteriophages as targeted vectors for efficient photodynamic killing of cancer cells. M13 was genetically refactored to display on the phage tip a peptide (SYPIPDT) able to bind the epidermal growth factor receptor (EGFR). The refactored M13(EGFR) phages demonstrated EGFR-targeted tropism and were internalized by A431 cancer cells, that overexpress EGFR. Using an orthogonal approach to the genetic display, M13(EGFR) phages were then chemically modified, conjugating hundreds of Rose Bengal (RB) photosensitizing molecules on the capsid surface, without affecting the selective recognition of the SYPIPDT peptides. Upon internalization, the M13(EGFR)-RB derivatives generated intracellularly reactive oxygen species, activated by an ultralow intensity white light irradiation. The killing activity of cancer cells is observed at picomolar concentrations of the M13(EGFR) phage.
外文关键词:CANCER-CELLS;GOLD NANOPARTICLES;FILAMENTOUS PHAGE;BACTERIOPHAG;PHOTOSENSITIZERS;THERAPEUTICS;RECOGNITION;PEPTIDES;TEMPLATE;DELIVERY
作者:Ulfo, L;Cantelli, A;Petrosino, A;Costantini, PE;Nigro, M;Starinieri, F;Turrini, E;Zadran, SK;Zuccheri, G;Saporetti, R;Di Giosia, M;Danielli, A;Calvaresi, M
作者单位:Alma Mater Studiorum Univ Bologna
期刊名称:NANOSCALE
期刊影响因子:6.895
出版年份:2021
出版刊次:
点击下载:M13噬菌体的正交纳米结构在受体靶向抗癌光动力疗法中的应用