Targeted cancer phototherapy using phthalocyanine–anticancer drug conjugates

Rennie, Chris C.; Edkins, Robert M.

doi:10.1039/d2dt02040h

Cited by 11 publications

(5 citation statements)

References 79 publications

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“…Due to its proper aromatic rings created by nitrogen atoms, it's frequently used to stain several biomolecules and it has quite absorption and emission properties [44]. Furthermore, novel approaches are using Phthalocyanine in the phototherapy treatment of tumors [45]. In addition, while there is no evidence pointing the interactions of Phthalocyanine with Cat D in literature, ligandprotein interaction analysis has shown that Phthalocyanine might interact with Cat D's ALA 13, ILE 134, MET 307, and MET 309 residues through pi-sulfur and pi-alkyl interactions, ASP 231 residue through pi-anion interactions.…”

Section: Resultsmentioning

confidence: 99%

Discovery of Repurposable Drugs in the Combination Therapy of Breast Cancer: A Virtual Drug Screening Study

KIRMIZIAY,

DEMİR,

ÖĞÜTÇÜ

et al. 2024

Turkish Computational and Theoretical Chemistry

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Cathepsin D (Cat D) is a lysosomal aspartic acid protease encoded by CTSD gene and has significant biological roles such as degradation of extracellular and intracellular proteins, regulation of apoptosis, hormone processing, antigen processing etc. Furthermore, it is overexpressed by breast cancer cells and it acts a role in many processes affecting the cancer prognosis such as metastasis, angiogenesis, invasion, and drug resistance through regulation of the metabolic pathways and digesting the extracellular matrix (ECM) proteins. Due to that there is no drug targeting Cat D in clinical trial phases, a virtual drug screening in order to reveal possible drugs with high Cat D inhibitory activity from a library composed of 12,111 ligands is carried out with this study. Results have demonstrated that ZINC000003922429 (Adozelesin), ZINC000012358610 (Phthalocyanine), ZINC000051951669 (Bemcentinib), ZINC000003786250 (YM022), and ZINC000150338819 (Ledipasvir) have high binding affinity to Cat D. Among these chemical ligands, YM022 from Drugs in Clinical Trials dataset has been evaluated as most promising one that might be repurposed in the treatment of breast cancer due to its high affinity, convenient ADME and Toxicity properties, and highest bioactivity profiles. However, the possible activity of YM022 should be analyzed with further molecular dynamics (MD) simulations, in vitro and in vivo studies.

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Section: Resultsmentioning

confidence: 99%

Discovery of Repurposable Drugs in the Combination Therapy of Breast Cancer: A Virtual Drug Screening Study

KIRMIZIAY,

DEMİR,

ÖĞÜTÇÜ

et al. 2024

Turkish Computational and Theoretical Chemistry

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“…Phthalocyanines, as a series of classical photosensitizers, have been widely concerned in PDT, but they still have the drawbacks of high phototoxicity and poor selectivity [ 50 ] Therefore, based on phthalocyanine molecules and nanosized phthalocyanines, the strategy of using activatable phthalocyanines can significantly improve the selectivity and reduce phototoxicity of phthalocyanines. [ 51 ] Activatable strategy means that the activity of phthalocyanine in healthy tissues is inhibited, and the activity is restored under the stimulation of various factors (such as pH, enzyme, nucleic acid, GSH).…”

Section: Design Strategiesmentioning

confidence: 99%

Innovative Design Strategies Advance Biomedical Applications of Phthalocyanines

Cai

Wang

et al. 2023

Adv Healthcare Materials

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Owing to their long absorption wavelengths, high molar absorptivity, and tunable photosensitivity, phthalocyanines have been widely used in photodynamic therapy (PDT). However, phthalocyanines still face the drawbacks of poor targeting, “always‐on” photosensitizing properties, and unsatisfactory therapeutic efficiency, which limit their wide applications in biomedical fields. Thus, new design strategies such as modification of targeting molecules, formation of nanoparticles, and activating photosensitizers are developed to improve the above defects. Notably, recent studies have shown that novel phthalocyanines are not only used in fluorescence imaging and PDT, but also in photoacoustic imaging, photothermal imaging, sonodynamic therapy, and photothermal therapy. This review focuses on recent design strategies, applications in biomedicine, and clinical development of phthalocyanines, providing ideas and references for the design and application of phthalocyanine, so as to promote their future transformation into clinical applications.

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“…In the type-II mechanism, a tripletexcited photosensitizer reacts with molecular oxygen to give highly reactive singlet oxygen, 1 O 2 , as reactive intermediate, which in turn oxidizes the DNA bases [46]. As a result, various classes of photosensitizers [47][48][49] have been established, for example, porphyrins [50], chlorins [51], phthalocyanines [52], porphycenes [53], metal-organic complexes [54][55][56], dye aggregates [57], as well as nano-drug carriers and metal-based nanoparticles [58,59]. But although these classes of compounds have been intensively studied and already contributed significantly to the field of PDT, there is still a demand for novel DNA-photodamaging ligands that could be applied for specific purposes, e.g., to improve efficacy or to limit side-effects.…”

Section: Introductionmentioning

confidence: 99%

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

Schlosser,

Fedorova,

Fedorov

et al. 2024

Beilstein J. Org. Chem.

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The photoreactions of selected styrylpyridine derivatives to the corresponding benzo[c]quinolizinium ions are described. It is shown that these reactions are more efficient in aqueous solution (97–44%) than in organic solvents (78–20% in MeCN). The quinolizinium derivatives bind to DNA by intercalation with binding constants of 6–11 × 104 M−1, as shown by photometric and fluorimetric titrations as well as by CD- and LD-spectroscopic analyses. These ligand–DNA complexes can also be established in situ upon irradiation of the styrylpyridines and formation of the intercalator directly in the presence of DNA. In addition to the DNA-binding properties, the tested benzo[c]quinolizinium derivatives also operate as photosensitizers, which induce DNA damage at relative low concentrations and short irradiation times, even under anaerobic conditions. Investigations of the mechanism of the DNA damage revealed the involvement of intermediate hydroxyl radicals and C-centered radicals. Under aerobic conditions, singlet oxygen only contributes to marginal extent to the DNA damage.

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Targeted cancer phototherapy using phthalocyanine–anticancer drug conjugates

Abstract: Phototherapy, the use of light to selectively ablate cancerous tissue, is a compelling prospect. Phototherapy is divided into two major domains: photodynamic and photothermal, whereby photosensitizer irradiation generates reactive oxygen...

Cited by 11 publications

References 79 publications

Discovery of Repurposable Drugs in the Combination Therapy of Breast Cancer: A Virtual Drug Screening Study

Discovery of Repurposable Drugs in the Combination Therapy of Breast Cancer: A Virtual Drug Screening Study

Innovative Design Strategies Advance Biomedical Applications of Phthalocyanines

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

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