Mitochondria‐Targeted Water‐Soluble Organic Nanoparticles of Chlorin Derivatives for Biocompatible Photodynamic Therapy

Abstract 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.