From Cancer to Infection: An amphiphilic ABAC Phthalocyanine for Versatile Phototherapy

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.

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BibTeX RIS

BibTeX

@misc{abraham2026from,
  title = {{From Cancer to Infection: An amphiphilic ABAC Phthalocyanine for Versatile Phototherapy}},
  author = {Jibin Alex Abraham and Monika Rohlickova and Magdalena Satranska Kozlikova and Jiri Demuth and Pavlina Vavrova and Klara Konecna and Petr Zimcik and Miloslav Machacek and Veronika Novakova},
  howpublished = {ChemRxiv},
  year = {2026},
  month = oct,
  doi = {10.26434/chemrxiv.15010492/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010492/v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - From Cancer to Infection: An amphiphilic ABAC Phthalocyanine for Versatile Phototherapy
AU  - Jibin Alex Abraham
AU  - Monika Rohlickova
AU  - Magdalena Satranska Kozlikova
AU  - Jiri Demuth
AU  - Pavlina Vavrova
AU  - Klara Konecna
AU  - Petr Zimcik
AU  - Miloslav Machacek
AU  - Veronika Novakova
PY  - 2026
DA  - 2026/10/15
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15010492/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010492/v1
AB  - 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.
ER  -

Abstract

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