Phthalocyanines Conjugated with Small Biologically Active Compounds for the Advanced Photodynamic Therapy: A Review

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range...

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Main Authors: Kyrylo Chornovolenko, Tomasz Koczorowski
Format: Article
Language:English
Published: MDPI AG 2025-08-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/15/3297
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author Kyrylo Chornovolenko
Tomasz Koczorowski
author_facet Kyrylo Chornovolenko
Tomasz Koczorowski
author_sort Kyrylo Chornovolenko
collection DOAJ
description Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds.
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spelling doaj-art-c11f03903ffb44f29224de2355773d7c2025-08-20T03:04:43ZengMDPI AGMolecules1420-30492025-08-013015329710.3390/molecules30153297Phthalocyanines Conjugated with Small Biologically Active Compounds for the Advanced Photodynamic Therapy: A ReviewKyrylo Chornovolenko0Tomasz Koczorowski1Chair and Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, PolandChair and Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, PolandPhthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds.https://www.mdpi.com/1420-3049/30/15/3297photodynamic therapyphotosensitizerphthalocyanineconjugatestargeted therapy
spellingShingle Kyrylo Chornovolenko
Tomasz Koczorowski
Phthalocyanines Conjugated with Small Biologically Active Compounds for the Advanced Photodynamic Therapy: A Review
Molecules
photodynamic therapy
photosensitizer
phthalocyanine
conjugates
targeted therapy
title Phthalocyanines Conjugated with Small Biologically Active Compounds for the Advanced Photodynamic Therapy: A Review
title_full Phthalocyanines Conjugated with Small Biologically Active Compounds for the Advanced Photodynamic Therapy: A Review
title_fullStr Phthalocyanines Conjugated with Small Biologically Active Compounds for the Advanced Photodynamic Therapy: A Review
title_full_unstemmed Phthalocyanines Conjugated with Small Biologically Active Compounds for the Advanced Photodynamic Therapy: A Review
title_short Phthalocyanines Conjugated with Small Biologically Active Compounds for the Advanced Photodynamic Therapy: A Review
title_sort phthalocyanines conjugated with small biologically active compounds for the advanced photodynamic therapy a review
topic photodynamic therapy
photosensitizer
phthalocyanine
conjugates
targeted therapy
url https://www.mdpi.com/1420-3049/30/15/3297
work_keys_str_mv AT kyrylochornovolenko phthalocyaninesconjugatedwithsmallbiologicallyactivecompoundsfortheadvancedphotodynamictherapyareview
AT tomaszkoczorowski phthalocyaninesconjugatedwithsmallbiologicallyactivecompoundsfortheadvancedphotodynamictherapyareview