Photosensitizers are central to the efficacy of photodynamic therapy (PDT) in cancer treatment. The phototoxic index (PI) defines the therapeutic window of a photosensitizer, with the clinically used Photosens® exhibiting a PI of 725. In our study, we observed that Zn(II) phthalocyanine mono-β-substituted with 4-carboxyphenoxy (ZnPc-COOH) displayed a phototoxic IC 50 in bladder cancer T24 cells at approximately 11.2 nM, yet its dark toxicity was notably high, yielding a PI of only 199. We hypothesize that the elevated dark toxicity is linked to mitochondrial localization. Rather than employing traditional side-chain substitution strategies to mitigate dark toxicity, we adopted a center metal substitution approach, synthesizing the first Al(III) phthalocyanine mono-β-substituted with 4-carboxyphenoxy photosensitizer (AlPc-COOH). Remarkably, AlPc-COOH localized to the lysosome, exhibited a phototoxic IC 50 of 1 nM, and showed a nearly 89-fold reduction in dark toxicity, achieving a PI of 223,700, which is 1000 times greater than ZnPc-COOH. In a murine orthotopic bladder cancer model, AlPc-COOH demonstrated therapeutic efficacy comparable to that of the clinically used chemotherapeutic agent mitomycin C (MMC). This study provides a crucial foundation for the design of optimized mono-substituted aluminum phthalocyanine-based photosensitizers.
Gang Xiang,Wensi Xu,Wenfeng Zhuge,Qing Huang,Cuizhong Zhang,Jinyun Peng
Isoniazid is a first-line drug used to treat tuberculosis. However, its excessive use can lead to serious adverse effects. Thus, strict monitoring of the isoniazid levels in medications and human systems is required. In this study, a new polymer (AlPc-TB POP) containing a metal phthalocyanine and Tröger's base was synthesized and explored as an electrocatalyst for the oxidation of isoniazid. The results indicated that the polymer is an excellent electron-transfer medium for isoniazid oxidation. The AlPc-TB POP-based sensor quantified isoniazid in the linear range of 0.1–130 μM, with a detection limit of 0.0185 μM. The response of the developed sensor to isoniazid was reproducible and stable. Furthermore, this method can accurately determine isoniazid levels by ignoring the influence of common interfering species in tablets and biological samples. This study contributes to the development of nitrogen-rich porous organic polymers and offers a novel strategy for addressing challenges in disease therapeutic efficacy and public safety monitoring.
Xiaobo Pan,Jin Xie,Zheng Li,Maxin Chen,Mengyan Wang,Pei-Nan Wang,Li Chen,Lan Mi
As a second-generation photodynamic therapy (PDT) photosensitizer, aluminum phthalocyanine chloride tetrasulfonate (Pc) has gained great attention due to its high absorption at the red light region. Yet, its application in PDT is strongly limited by its low cellular uptake efficiency. In this report, nitrogen-doped TiO 2 nanoparticles (N–TiO 2 ) conjugated with Pc are synthesized by a two-step surface modification method. The N–TiO 2 –Pc products are characterized by Zeta potential, transmission electron microscopy and UV–vis absorption spectroscopy. The cellular uptake, intracellular distribution, cytotoxicity and the photokilling effect of the nanoparticles are studied on different cancer cell lines. Compared with Pc, the absorption spectrum of N–TiO 2 –Pc expands from red to UV region, resulting in a higher production of reactive oxygen species under visible light irradiation. In addition, the cellular uptake of Pc is largely improved by its carrier N–TiO 2 . The photokilling efficiency of N–TiO 2 –Pc is over ten times higher than that of Pc. The results suggest that N–TiO 2 –Pc is an excellent candidate as a photosensitizer in PDT.
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