Physics Department, Taras Shevchenko National University of Kyiv, 60 Volodymyrska Str., 01601 Kyiv, Ukraine.
Chemistry Department, Taras Shevchenko National University of Kyiv, 60 Volodymyrska Str., 01601 Kyiv, Ukraine.
Molecules. 2024 May 9;29(10):2224. doi: 10.3390/molecules29102224.
Photodynamic therapy (PDT) is a non-invasive anticancer treatment that uses special photosensitizer molecules (PS) to generate singlet oxygen and other reactive oxygen species (ROS) in a tissue under excitation with red or infrared light. Though the method has been known for decades, it has become more popular recently with the development of new efficient organic dyes and LED light sources. Here we introduce a ternary nanocomposite: water-soluble star-like polymer/gold nanoparticles (AuNP)/temoporfin PS, which can be considered as a third-generation PDT system. AuNPs were synthesized in situ inside the polymer molecules, and the latter were then loaded with PS molecules in an aqueous solution. The applied method of synthesis allows precise control of the size and architecture of polymer nanoparticles as well as the concentration of the components. Dynamic light scattering confirmed the formation of isolated particles (120 nm diameter) with AuNPs and PS molecules incorporated inside the polymer shell. Absorption and photoluminescence spectroscopies revealed optimal concentrations of the components that can simultaneously reduce the side effects of dark toxicity and enhance singlet oxygen generation to increase cancer cell mortality. Here, we report on the optical properties of the system and detailed mechanisms of the observed enhancement of the phototherapeutic effect. Combinations of organic dyes with gold nanoparticles allow significant enhancement of the effect of ROS generation due to surface plasmonic resonance in the latter, while the application of a biocompatible star-like polymer vehicle with a dextran core and anionic polyacrylamide arms allows better local integration of the components and targeted delivery of the PS molecules to cancer cells. In this study, we demonstrate, as proof of concept, a successful application of the developed PDT system for in vitro treatment of triple-negative breast cancer cells under irradiation with a low-power LED lamp (660 nm). We consider the developed nanocomposite to be a promising PDT system for application to other types of cancer.
光动力疗法（PDT）是一种非侵入性的抗癌治疗方法，它利用特殊的光敏剂分子（PS）在红光或红外光激发下，在组织中产生单线态氧和其他活性氧物质（ROS）。尽管这种方法已经存在了几十年，但随着新型高效有机染料和 LED 光源的发展，它最近变得越来越流行。在这里，我们介绍了一种三元纳米复合材料：水溶性星形聚合物/金纳米粒子（AuNP）/替莫泊芬 PS，它可以被认为是第三代 PDT 系统。AuNP 是在聚合物分子内原位合成的，然后在水溶液中负载 PS 分子。这种合成方法可以精确控制聚合物纳米粒子的尺寸和结构以及各组分的浓度。动态光散射证实了形成了孤立的颗粒（直径 120nm），其中包含 AuNP 和 PS 分子。吸收和光致发光光谱揭示了各组分的最佳浓度，这些浓度可以同时减少暗毒性的副作用，并增强单线态氧的产生，从而提高癌细胞的死亡率。在这里，我们报告了该系统的光学性质以及观察到的光疗效果增强的详细机制。由于后者的表面等离子体共振，有机染料与金纳米粒子的组合允许显著增强 ROS 生成的效果，而应用具有葡聚糖核和阴离子聚丙烯酰胺臂的生物相容性星形聚合物载体允许更好地局部整合各组分并将 PS 分子靶向递送到癌细胞。在这项研究中，我们证明了，作为概念验证，所开发的 PDT 系统在低功率 LED 灯（660nm）照射下对三阴性乳腺癌细胞进行体外治疗的成功应用。我们认为所开发的纳米复合材料是一种很有前途的 PDT 系统，可应用于其他类型的癌症。
