Pasparakis George, Manouras Theodore, Vamvakaki Maria, Argitis Panagiotis
1] Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology-Hellas (FORTH), PO Box 1527, 71110 Heraklion, Crete, Greece [2] University College London, School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK [3].
1] Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology-Hellas (FORTH), PO Box 1527, 71110 Heraklion, Crete, Greece [2] Institute of Nanoscience and Nanotechnology, NCSR Demokritos, 15310 Aghia Paraskevi, Attiki, Greece [3].
Nat Commun. 2014 Apr 7;5:3623. doi: 10.1038/ncomms4623.
Light-controlled drug delivery systems constitute an appealing means to direct and confine drug release spatiotemporally at the site of interest with high specificity. However, the utilization of light-activatable systems is hampered by the lack of suitable drug carriers that respond sharply to visible light stimuli at clinically relevant wavelengths. Here, a new class of self-assembling, photo- and pH-degradable polymers of the polyacetal family is reported, which is combined with photochemical internalization to control the intracellular trafficking and release of anticancer compounds. The polymers are synthesized by simple and scalable chemistries and exhibit remarkably low photolysis rates at tunable wavelengths over a large range of the spectrum up to the visible and near infrared regime. The combinational pH and light mediated degradation facilitates increased therapeutic potency and specificity against model cancer cell lines in vitro. Increased cell death is achieved by the synergistic activity of nanoparticle-loaded anticancer compounds and reactive oxygen species accumulation in the cytosol by simultaneous activation of porphyrin molecules and particle photolysis.
光控药物递送系统是一种很有吸引力的手段，能够以高特异性在感兴趣的部位进行时空定向和限制药物释放。然而，由于缺乏在临床相关波长下对可见光刺激有敏锐响应的合适药物载体，光激活系统的应用受到了阻碍。在此，报道了一类新型的聚缩醛家族自组装、光和pH可降解聚合物，其与光化学内化相结合以控制抗癌化合物的细胞内运输和释放。这些聚合物通过简单且可扩展的化学方法合成，并且在高达可见光和近红外区域的大范围光谱内的可调波长下表现出极低的光解速率。pH和光介导的组合降解促进了体外对模型癌细胞系治疗效力和特异性的提高。通过负载纳米颗粒的抗癌化合物的协同活性以及通过卟啉分子的同时激活和颗粒光解使活性氧在细胞质中积累，实现了细胞死亡的增加。
