Rational design of a lysosome-targeting and near-infrared absorbing Ru(<scp>ii</scp>)–BODIPY conjugate for photodynamic therapy

Qiao, Liping; Liu, Jiangping; Han, Yunhong; Wei, Fangmian; Liao, Xinxing; Zhang, Cheng; Xie, Lina; Ji, Liang‐Nian; Chao, Hui

doi:10.1039/d0cc06926d

Cited by 38 publications

(31 citation statements)

References 16 publications

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“…As a result, several studies investigated the effects of utilizing organelle targeted PSs, which localize to nucleus, mitochondria or lysosomes ( Karaman et al, 2019 ; Ucar et al, 2019 ). Indeed, such approaches might improve the outcome of PDT ( Wan et al, 2020 ; Qiao et al, 2021 ). According to the literature, mitochondria-targeting groups ( e.g.…”

Section: Novel Approaches To Improve Outcomementioning

confidence: 99%

Photodynamic Therapy—Current Limitations and Novel Approaches

2021

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Photodynamic therapy (PDT) mostly relies on the generation of singlet oxygen, via the excitation of a photosensitizer, so that target tumor cells can be destroyed. PDT can be applied in the settings of several malignant diseases. In fact, the earliest preclinical applications date back to 1900’s. Dougherty reported the treatment of skin tumors by PDT in 1978. Several further studies around 1980 demonstrated the effectiveness of PDT. Thus, the technique has attracted the attention of numerous researchers since then. Hematoporphyrin derivative received the FDA approval as a clinical application of PDT in 1995. We have indeed witnessed a considerable progress in the field over the last century. Given the fact that PDT has a favorable adverse event profile and can enhance anti-tumor immune responses as well as demonstrating minimally invasive characteristics, it is disappointing that PDT is not broadly utilized in the clinical setting for the treatment of malignant and/or non-malignant diseases. Several issues still hinder the development of PDT, such as those related with light, tissue oxygenation and inherent properties of the photosensitizers. Various photosensitizers have been designed/synthesized in order to overcome the limitations. In this Review, we provide a general overview of the mechanisms of action in terms of PDT in cancer, including the effects on immune system and vasculature as well as mechanisms related with tumor cell destruction. We will also briefly mention the application of PDT for non-malignant diseases. The current limitations of PDT utilization in cancer will be reviewed, since identifying problems associated with design/synthesis of photosensitizers as well as application of light and tissue oxygenation might pave the way for more effective PDT approaches. Furthermore, novel promising approaches to improve outcome in PDT such as selectivity, bioengineering, subcellular/organelle targeting, etc. will also be discussed in detail, since the potential of pioneering and exceptional approaches that aim to overcome the limitations and reveal the full potential of PDT in terms of clinical translation are undoubtedly exciting. A better understanding of novel concepts in the field (e.g. enhanced, two-stage, fractional PDT) will most likely prove to be very useful for pursuing and improving effective PDT strategies.

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Section: Novel Approaches To Improve Outcomementioning

confidence: 99%

Photodynamic Therapy—Current Limitations and Novel Approaches

2021

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“…One strategy is to introduce a heavy atom on the 2,6 positions of the BODIPY core to facilitate the ISC and populate the triplet excited state . So far, multiple studies have been done on various BODIPY–metal complexes including those of Ru(II), − Re(I), , Pt(II), − Ir(III), and Co(II) , with different applications, mainly focused on PDT and photocatalysis. To the best of our knowledge, the Mn–BODIPY complex, with potential application in PDT, has yet to be reported.…”

Section: Introductionmentioning

confidence: 99%

Release of CO and Production of ¹O₂ from a Mn-BODIPY Photoactivated CO Releasing Molecule with Visible Light

2021

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Carbon monoxide (CO) is shown to enhance the sensitivity of cancer cells to generate reactive oxygen species such as singlet oxygen ( 1 O 2 ) from chemotherapeutics and reduce the drug resistance. Herein, we introduced two Mn-based photoactivated CO releasing molecules conjugated with an emissive BODIPY (BDP) moiety with a general formula of Mn(CO) 3 (bpy-R-BDP)Br (R = H or I), labeled as Mn-bpy-H-BDP and Mn-bpy-I-BDP. While both complexes release CO with visible light, Mn-bpy-I-BDP releases CO and produces 1 O 2 from a single molecule. In addition to 1 O 2 generation, iodination of BDP red shifts the absorption of Mn-bpy-I-BDP further into the visible region and significantly increases the dark stability of the complex. Cyclic voltammetry and density functional theory (DFT) calculations suggest a Mn-based highest occupied molecular orbital (HOMO) and a BDP-based lowest unoccupied molecular orbital (LUMO) in these complexes. However, time-dependent DFT calculations suggest that the HOMO − 2(π BDP ) → LUMO(π BDP * ) is the main optical transition upon excitation with visible light in both complexes. The presence of a phosphorescence peak from the triplet excited state of bpy-I-BDP in both the free ligand and its Mn complex at 77 K was used as additional evidence for 1 O 2 production. We also probed formation of photo-intermediates and products during photolysis with Fourier-transform infrared, 1 H NMR, emission, and absorption experiments and DFT calculations.

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“…For example, trimer 12 triggers cell death through apoptosis only after irradiation. 19 The average percentage of early and late apoptotic cell population increased from 30.5% to 90.1% when the the dye concentration was increased from 2.84 μM [IC 50 (see Figure 4 )] to 5.00 μM. In contrast, the percentage of necrotic cells was not significant in either case, thus confirming apoptotic cell death (see Figure S13 ).…”

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confidence: 85%

Development of Geometry-Controlled All-Orthogonal BODIPY Trimers for Photodynamic Therapy and Phototheragnosis

et al. 2022

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We have established an easy synthetic protocol for selectively developing all-orthogonal BODIPY trimers with unprecedented geometries on the basis of selecting methyl oxidation versus electrophilic formylation of key dimeric precursors. Photophysical characterization together with biological assays unraveled the most suitable BODIPY–BODIPY geometrical arrangements within the trimer, forcing them to serve as molecular platforms for the development of new, advanced heavy-atom-free photosensitizers for photodynamic therapy and phototheragnosis.

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Rational design of a lysosome-targeting and near-infrared absorbing Ru(ii)–BODIPY conjugate for photodynamic therapy

Abstract: A lysosome-targeting and near-infrared absorbing Ru(ii)–BODIPY conjugate exhibits prominent tumor inhibitory efficiency in malignant melanoma A375 cells and in vivo experiments.

Cited by 38 publications

References 16 publications

Photodynamic Therapy—Current Limitations and Novel Approaches

Photodynamic Therapy—Current Limitations and Novel Approaches

Release of CO and Production of ¹O₂ from a Mn-BODIPY Photoactivated CO Releasing Molecule with Visible Light

Development of Geometry-Controlled All-Orthogonal BODIPY Trimers for Photodynamic Therapy and Phototheragnosis

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Rational design of a lysosome-targeting and near-infrared absorbing Ru(ii)–BODIPY conjugate for photodynamic therapy

Abstract: A lysosome-targeting and near-infrared absorbing Ru(ii)–BODIPY conjugate exhibits prominent tumor inhibitory efficiency in malignant melanoma A375 cells and in vivo experiments.

Cited by 38 publications

References 16 publications

Photodynamic Therapy—Current Limitations and Novel Approaches

Photodynamic Therapy—Current Limitations and Novel Approaches

Release of CO and Production of 1O2 from a Mn-BODIPY Photoactivated CO Releasing Molecule with Visible Light

Development of Geometry-Controlled All-Orthogonal BODIPY Trimers for Photodynamic Therapy and Phototheragnosis

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Release of CO and Production of ¹O₂ from a Mn-BODIPY Photoactivated CO Releasing Molecule with Visible Light