Hamza Hady, Schifano Veronica, Colciago Giorgia, Ortenzi Marco Aldo, Ferretti Anna Maria, Di Carlo Gabriele, Dozzi Maria Vittoria, Vago Riccardo, Tessore Francesca, Maggioni Daniela
Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20123 Milano, Italy.
Chemistry Department, Faculty of Science, Alexandria University, P.O. Box 21568, Alexandria, Egypt.
Nanoscale. 2025 Aug 15;17(32):18935-18947. doi: 10.1039/d5nr01078k.
The development of effective drug delivery systems represents a significant advancement in cancer treatment. Anisotropic, natural, and cost-effective nano-vectors, such as halloysite nanotubes (HNT), can be utilized for this purpose. In this study, we loaded the HNT with the apolar photosensitizers (PS) 5,10,15,20-tetrakis(perfluorophenyl)porphyrin (HTPPF) and its Zn(II) complex (ZnTPPF) to produce singlet oxygen for photodynamic therapy (PDT). The loading was achieved through repeated vacuum/N cycles using both pristine HNT and HNT modified with tetradecylphosphonic acid (HNT-TDP) to promote the uptake of the lipophilic PS in the inner lumen. To slow down the release of PS from HNT, the nanotubes were treated with dextrin. The ability of the free base and Zn perfluorinated porphyrins to produce singlet oxygen (O) was confirmed by irradiating the samples with a low-power visible LED emitter (23 mW cm), showing a O quantum yield of 22% and 34%, respectively, in ethanol. The characterization of the nanocomposite is not trivial, so we employed a wide range of analytical techniques to investigate the material thoroughly, particularly the location of PS within the HNT. All nano-hybrids were analyzed by attenuated total reflectance infrared (ATR-FTIR), diffuse reflectance (DRS) and solid-state emission spectroscopy. Thermogravimetric analysis (TGA) was used to determine the loading capacity of HNT. To better understand the interactions between the PS and the nanoclay, we compared all the loaded HNT samples with mechanically mixed HNT and solid HTPPF or ZnTPPF samples, where the interaction with the HNT inner lumen is assumed to be absent. We measured the release kinetics using UV-vis spectroscopy, observing a delayed release of the PS. Finally, we studied the cellular uptake of pristine HNT and a loaded sample (HNT-TDP-HTPPF-dextrin) by confocal microscopy using three distinct tumor cell lines. The cytotoxicity on PC3, 5637 and UMUC3 cells was then assessed as reduction of cell viability both on cells left in the dark and those irradiated with a visible light emitting LED (1.3 mW cm), ascertaining the ability to induce cell death especially after light administration.
有效的药物递送系统的发展代表了癌症治疗的重大进步。各向异性、天然且具有成本效益的纳米载体，如埃洛石纳米管（HNT），可用于此目的。在本研究中，我们将非极性光敏剂（PS）5,10,15,20-四（全氟苯基）卟啉（HTPPF）及其锌（II）配合物（ZnTPPF）负载到HNT中，以产生单线态氧用于光动力疗法（PDT）。通过使用原始HNT和用十四烷基膦酸改性的HNT（HNT-TDP）进行重复的真空/氮气循环来实现负载，以促进亲脂性PS在内腔中的摄取。为了减缓PS从HNT中的释放，纳米管用糊精进行了处理。通过用低功率可见LED发射器（23 mW/cm²）照射样品，证实了游离碱和锌全氟卟啉产生单线态氧（¹O₂）的能力，在乙醇中¹O₂的量子产率分别为22%和34%。纳米复合材料的表征并非易事，因此我们采用了广泛的分析技术来全面研究该材料，特别是PS在HNT中的位置。所有纳米杂化物均通过衰减全反射红外（ATR-FTIR）、漫反射（DRS）和固态发射光谱进行分析。热重分析（TGA）用于确定HNT的负载量。为了更好地理解PS与纳米粘土之间的相互作用，我们将所有负载的HNT样品与机械混合的HNT以及固体HTPPF或ZnTPPF样品进行了比较，在后者中假定不存在与HNT内腔的相互作用。我们使用紫外可见光谱测量了释放动力学，观察到PS的延迟释放。最后，我们通过共聚焦显微镜使用三种不同的肿瘤细胞系研究了原始HNT和负载样品（HNT-TDP-HTPPF-糊精）的细胞摄取。然后评估了对PC3、5637和UMUC3细胞的细胞毒性，即对处于黑暗中的细胞以及用可见光发射LED（1.3 mW/cm²）照射的细胞的细胞活力降低情况，确定了尤其是在光照后诱导细胞死亡的能力。
