Year: 2026
Type: preprint
Abstract: The development of photosensitizers capable of operating across multiple therapeutic photoprocesses remains a major challenge in photomedicine. Herein, we report a cationic amphiphilic ABAC zinc(II) phthalocyanine (ZnPc-Me) obtained by a direct [3+1] mixed cyclization strategy followed by post-functional quaternization/transalkylation. The controlled amphiphilic architecture promotes optimal membrane anchoring while suppressing aggregation in lipid environments. Due to its optimized physico-chemical and photophysical properties, ZnPc-Me acts as a multimodal photodynamic platform whose biological activity can be switched between photodynamic therapy (PDT), vascular-targeted PDT, photodynamic inactivation (PDI) or photochemical internalization (PCI) by adjusting the administration, irradiation and dosing protocols. The compound exhibits high activity in cancer models (with EC50 in nM), surpasses clinically used photosensitizers under identical conditions, and retains activity in 3D tumor spheroids. In parallel, it efficiently inactivates multidrug-resistant ESKAPE pathogens and enables photochemical internalization of a model drug through both light-before and light-after protocols, producing dose-dependent synergistic effects. Despite its high photodynamic efficacy, ZnPc-Me shows negligible dark toxicity, no hemolysis, and no epidermal penetration, ensuring a favorable safety profile for both topical and systemic applications. Overall, this work introduces a versatile design strategy for amphiphilic phthalocyanines that enables adaptive photodynamic activity across diverse biomedical applications, opening new avenues for the development of multifunctional light-responsive therapeutic systems.
Source: ChemRxiv
Institutions: Charles University, University of Hradec Králové
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7221940614