Department of Materials Science and Engineering, Kroto Research Institute, University of Sheffield, Sheffield, United Kingdom.
Department of Oncology & Metabolism, The Medical School, University of Sheffield, Sheffield, United Kingdom.
PLoS One. 2019 Jul 25;14(7):e0220210. doi: 10.1371/journal.pone.0220210. eCollection 2019.
Photodynamic therapy (PDT) uses photosensitisers such as protoporphyrin IX (PpIX) to target tumours via the release of toxic singlet oxygen when irradiated. The effectivity of the treatment is limited by the innate properties of the photosensitizers; they typically exhibit inefficient accumulation in target tissue and high dark toxicity. Carbon dots (CDs) are biocompatible fluorescent nanoparticles which can improve PpIX cellular uptake and solubility. In this work, we present conjugates synthesised by host-guest encapsulation (PpIX@CD) and amide cross-linking (PpIX-CD). Characterization demonstrated conjugates have a loading efficiency of 34-48% and similar singlet oxygen production to PpIX. PpIX-containing CDs showed a 2.2 to 3.7-fold decrease in dark toxicity. PpIX-CD and PpIX@CD showed equivalent light-induced toxicity to PpIX in concentrations >1 μg/ml, leading to a 3.2 to 4.1-fold increase in photo-toxicity index (PI). The less soluble fraction of cross-linked conjugates (PpIX-CD)p did not show significant difference from PpIX. Confocal light scanning microscopy demonstrated rapid intracellular uptake and accumulation of conjugates. Our results demonstrate the variations between cross-linking strategies in CD-based conjugates, highlighting their potential as carriers in drug delivery and bioimaging applications.
光动力疗法 (PDT) 使用原卟啉 IX (PpIX) 等光敏剂，通过辐照时释放有毒的单线态氧来靶向肿瘤。治疗的效果受到光敏剂固有特性的限制；它们通常在靶组织中的积累效率低，暗毒性高。碳点 (CDs) 是生物相容性的荧光纳米粒子，可以提高 PpIX 的细胞摄取和溶解度。在这项工作中，我们提出了通过主客体包封 (PpIX@CD) 和酰胺交联 (PpIX-CD) 合成的缀合物。表征表明，缀合物的载药效率为 34-48%，与 PpIX 产生的单线态氧相似。含 PpIX 的 CDs 在黑暗毒性方面降低了 2.2 到 3.7 倍。在浓度大于 1μg/ml 时，PpIX-CD 和 PpIX@CD 与 PpIX 具有等效的光诱导毒性，导致光毒性指数 (PI) 增加了 3.2 到 4.1 倍。交联缀合物的不溶性部分 (PpIX-CD)p 与 PpIX 没有显著差异。共聚焦光扫描显微镜显示了缀合物在细胞内的快速摄取和积累。我们的结果表明，CD 基缀合物中交联策略的变化，突出了它们在药物传递和生物成像应用中的载体潜力。
