Faculty of Chemistry, Jagiellonian University, Kraków 30-387, Poland.
Doctoral School of Exact and Natural Sciences, Jagiellonian University, Kraków 30-348, Poland.
ACS Appl Mater Interfaces. 2024 Sep 18;16(37):48937-48954. doi: 10.1021/acsami.4c04138. Epub 2024 Sep 6.
Two phthalocyanine derivatives tetra-peripherally substituted with -butylsulfonyl groups and coordinating either zinc(II) or platinum(II) ions have been synthesized and subsequently investigated in terms of their optical and photochemical properties, as well as biological activity in cellular, tissue-engineered, and animal models. Our research has revealed that both synthesized phthalocyanines are effective generators of reactive oxygen species (ROS). demonstrated an outstanding ability to generate singlet oxygen (Φ = 0.87-0.99), while in addition to O (Φ = 0.45-0.48) generated efficiently other ROS, in particular ·OH. Considering future biomedical applications, the affinity of the tested phthalocyanines for biological membranes (partition coefficient; log ) and their primary interaction with serum albumin were also determined. To facilitate their biological administration, a water-dispersible formulation of these phthalocyanines was developed using Pluronic triblock copolymers to prevent self-aggregation and improve their delivery to cancer cells and tissues. The results showed a significant increase in cellular uptake and phototoxicity when phthalocyanines were incorporated into the customizable polymeric micelles. Moreover, the improved distribution in the body and photodynamic efficacy of the encapsulated phthalocyanines were investigated in hiPSC-delivered organoids and BALB/c mice bearing CT26 tumors. Both photosensitizers exhibit strong antitumor activity. Notably, vascular-targeted photodynamic therapy (V-PDT) led to complete tumor eradication in 84% of and 100% of treated mice, and no recurrence has so far been observed for up to five months after treatment. In the case of PtSOBu, the effect was significantly stronger, offering a wider range of light doses suitable for achieving effective PDT.
已经合成了两个四外围取代有 - 丁基砜基并配位锌（II）或铂（II）离子的酞菁衍生物，并随后研究了它们的光学和光化学性质，以及在细胞、组织工程和动物模型中的生物活性。我们的研究表明，这两种合成的酞菁都是有效的活性氧（ROS）生成剂。 被证明是生成单线态氧（Φ = 0.87-0.99）的出色能力，而 除了 O（Φ = 0.45-0.48）之外，还有效地生成了其他 ROS，特别是·OH。考虑到未来的生物医学应用，还确定了测试的酞菁对生物膜的亲和力（分配系数；log ）及其与血清白蛋白的主要相互作用。为了便于它们的生物给药，使用 Pluronic 三嵌段共聚物开发了这些酞菁的水分散制剂，以防止自聚集并改善它们向癌细胞和组织的递送。结果表明，当酞菁被整合到可定制的聚合物胶束中时，细胞摄取和光毒性显著增加。此外，还研究了包裹的酞菁在 hiPSC 递送的类器官和携带 CT26 肿瘤的 BALB/c 小鼠中的体内分布和光动力疗效。两种光敏剂都表现出很强的抗肿瘤活性。值得注意的是，血管靶向光动力疗法（V-PDT）导致 84%的 和 100%的治疗小鼠完全消除肿瘤，并且在治疗后长达五个月的时间内没有复发。在 PtSOBu 的情况下，效果明显更强，提供了更广泛的适合实现有效 PDT 的光剂量范围。
Zotero 插件
