Photodynamic therapy (PDT) is a promising non‐invasive cancer therapy without any side‐effects. The photosensitizers (PSs) used in PDT are usually hydrophobic and not soluble in water. Water‐soluble PSs have been rarely studied in PDT research. Therefore, preparing water‐soluble PSs for clinical trials in PDT remains challenging. Here, we prepared water‐soluble organic nanoparticles (WSONs) using the following three chlorin derivatives: methyl pyropheophorbide a (MPPa), zinc metal‐introduced MPPa, and purpurin‐18 methyl ester. We used a very simple co‐precipitation method to develop WSONs through nanoprecipitation (solvent‐exchange) from THF to water. In this method, WSONs were developed in 87–112 nm sizes, based on TEM, with good water solubility and high water stability for more than a month. We evaluated intracellular accumulation and cell viability of these WSONs, exhibiting PDT results comparable to that of free PSs using HeLa cells. All WSONs were accumulated in mitochondria to induce mitochondria‐mediated apoptosis via effective PDT activity. This result is important not only for preparing WSONs with hydrophobic PSs to form highly water‐soluble PSs having good water stability in nanometre size, but also for retaining PDT activity with reduced dark toxicity, enabling potential applications for biocompatible PDT.

中文翻译：

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线粒体靶向氯代衍生物的水溶性有机纳米颗粒，用于生物相容性光动力疗法

光动力疗法（PDT）是一种有前途的无创癌症疗法，无任何副作用。PDT中使用的光敏剂（PSs）通常是疏水性的，不溶于水。在PDT研究中很少研究水溶性PS。因此，为在PDT中进行临床试验制备水溶性PS仍然具有挑战性。在这里，我们使用以下三种二氢卟酚衍生物制备了水溶性有机纳米粒子（WSON）：甲基焦脱镁叶绿酸a（MPPa），金属锌引入的MPPa和紫嘌呤18甲酯。我们使用一种非常简单的共沉淀方法，通过从THF到水的纳米沉淀（溶剂交换）来开发WSON。在这种方法中，基于TEM开发了WSON，尺寸为87-112 nm，具有良好的水溶性和高水稳定性，可使用一个月以上。我们评估了这些WSON的细胞内积累和细胞活力，显示出与使用HeLa细胞的游离PS相当的PDT结果。所有WSON都聚集在线粒体中，以通过有效的PDT活性诱导线粒体介导的细胞凋亡。该结果不仅对于制备具有疏水性PS的WSON以形成在纳米级具有良好水稳定性的高度水溶性PS十分重要，而且对于保持PDT活性并降低暗毒性也很重要，从而使生物相容性PDT的潜在应用成为可能。