Photodynamic therapy (PDT) is a promising non-invasive cancer treatment, but its efficacy depends on photosensitizer performance. Porphyrin-based photosensitizers face challenges including poor water solubility, limited photodynamic effects, and weak near-infrared absorption. In this study, a new conjugated porphyrin (Por) was synthesized by coupling zinc porphyrin with pyridine through alkyne bonds. The hydrophilic polyethylene glycol (PEG) chains were incorporated into the porphyrin framework to enhance the biocompatibility of organic compounds. After methylation or coordination with trans-platinum, two ionized porphyrin derivatives (Pt-Por and I-Por) were obtained, which exhibited enhanced photodynamic effect due to the introduction of heavy atoms such as iodine and platinum, increasing the probability of intersystem crossing (ISC). Under a 690 nm laser, I-Por and Pt-Por displayed high photodynamic effect with singlet oxygen quantum yields of 0.91 and 0.48, respectively. The biocompatibility and photocytotoxicity were evaluated using the Cell Counting Kit-8 (CCK-8) assay against Hepa1-6 cells. Both I-Por and Pt-Por exhibited significant phototherapeutic efficacy. The intracellular uptake and location of I-Por and Pt-Por were confirmed by confocal laser microscopy. Importantly, I-Por achieved a singlet oxygen quantum yield of 0.91, which is remarkably higher than that of Por (0.07) and exceeds the typical range of 0.5-0.8 reported for many porphyrin-based photosensitizers. Pt-Por exhibited very low dark cytotoxicity, maintaining cell viability above 90% at 50 μM. Thus, I-Por serves as a highly efficient photosensitizer due to its superior singlet oxygen generation, and Pt-Por is a promising candidate with very low dark cytotoxicity.
Wang et al. (2026) studied this question.