光动力疗法（PDT）是一种消除受损生物材料和细胞的有趣方式。该治疗利用了只有在受光照射时才活性的光敏分子的特性。本研究利用了超菊酯（hypericin）的双重性质，超菊酯是一种具有高光诊断和光动力疗法性能的亲脂分子。非荧光和光动力不活跃形式的超菊酯聚集体被载入SBA-15硅胶纳米孔中。合成的颗粒经过红外光谱、热重分析、差热分析、小角X射线散射和透射电子显微镜表征。通过吸收光谱和短寿命荧光证实了超菊酯聚集体的存在。在模拟生理条件下观察到超菊酯从颗粒中向血清蛋白释放的现象。温度和时间依赖性的超菊酯摄取研究显示了超菊酯从颗粒中逐渐释放并通过内吞作用主动转运进入癌细胞。通过荧光寿命成像对SBA-15-超菊酯的摄取进行细致观察，结果显示聚集态超菊酯分子（荧光寿命约4纳秒）在细胞摄取后仍存在于SBA-15颗粒中。然而，将超菊酯单聚体化后可以延长其荧光寿命约8纳秒，而且此过程在脂质区和细胞质膜中更为明显。这可能预示了整个荷载物的生物活性被延迟，这一观察结果在体外有效的光动力疗法中得到了证实。总之，本研究提出了一种安全无害的超菊酯传递方法，该方法在细胞和组织的靶位点激活超菊酯。Copyright © 2023 Elsevier B.V. All rights reserved.

Photodynamic therapy (PDT) represents an interesting modality for the elimination of damaged biomaterials and cells. This treatment takes advantage of the photosensitizing properties of molecules that are active only when irradiated with light. In the present work, a dual property of hypericin, a hydrophobic molecule with high performance in photodiagnostics and photodynamic therapy, was exploited. The non-fluorescent and photodynamically inactive form of hypericin aggregates was loaded into the nanopores of SBA-15 silica particles. The synthesized particles were characterized by infrared spectroscopy, thermogravimetry, differential thermal analysis, small-angle X-ray scattering and transmission electron microscopy. Hypericin aggregates were confirmed by absorption spectra typical of aggregated hypericin and by its short fluorescence lifetime. Release of hypericin from the particles was observed toward serum proteins, mimicking physiological conditions. Temperature- and time-dependent uptake of hypericin by cancer cells showed gradual release of hypericin from the particles and active cellular transport by endocytosis. A closer examination of SBA-15-hypericin uptake by fluorescence lifetime imaging showed that aggregated hypericin molecules, characterized by a short fluorescence lifetime (∼4 ns), were still present in the SBA-15 particles upon uptake by cells. However, monomerization of hypericin in cancer cells was observed by extending the hypericin fluorescence lifetime by ∼8 ns, preferentially in lipid compartments and the plasma membrane. This suggests a promising prognosis for delayed biological activity of the entire cargo, which was confirmed by effective PDT in vitro. In summary, this work presents an approach for safe, inactive delivery of hypericin that is activated at the target site in cells and tissues.Copyright © 2023 Elsevier B.V. All rights reserved.