Photochemical internalization (PCI) of bleomycin is equally effective in two dissimilar leiomyosarcoma xenografts in athymic mice

Sellevold, Simen; Peng, Qian; Fremstedal, Ane Sofie Viset; Berg, Kristian

doi:10.1016/j.pdpdt.2017.08.015

Cited by 4 publications

(4 citation statements)

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“…22 Fimaporfin-based PCI has also been shown to enhance the cytotoxic effect of BLM in rat bladder cancer cells 23 and in clinically relevant animal model studies. 24,25 PCI is currently also investigated for use as a vaccine therapy for cancer indications. [26][27][28] In the present study we aimed to elucidate the molecular mechanisms underlying fimaporfin-enhanced BLM toxicity in the AY-27 rat bladder cancer cell line in more detail by employing stable isotope labelling by amino acids in cell culture (SILAC)-based quantitative proteomics.…”

Section: Introductionmentioning

confidence: 99%

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Proteomic analysis reveals mechanisms underlying increased efficacy of bleomycin by photochemical internalization in bladder cancer cells

Gederaas,

Sharma,

Mbarak

et al. 2023

Mol. Omics

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Proteomic analysis reveals mechanisms underlying increased efficacy of bleomycin by photochemical internalization in bladder cancer cells

Gederaas,

Sharma,

Mbarak

et al. 2023

Mol. Omics

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“…This delivery strategy is very promising for Bleomycin. Several studies are now investigating Bleomycin and various photosensitizers in combination to perform photochemical internalization [ 23 , 28 , 29 , 30 , 31 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Photochemical Internalization with Fimaporfin: Enhanced Bleomycin Treatment for Head and Neck Cancer

Enzian,

Rahmanzadeh

2023

Pharmaceutics

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Head and neck squamous cell carcinoma (HNSCC) still represents the world’s sixth most common tumor entity, with increasing incidence. The reachability of light makes HNSCC suitable for light-based therapies such as Photochemical Internalization (PCI). The drug Bleomycin is cytotoxic and used as an anti-tumor medication. Since Bleomycin is endocytosed as a relatively large molecule, part of it is degraded in lysosomes before reaching its intracellular target. The goal of our study was to improve the intracellular availability of Bleomycin with PCI. We investigate the intracellular delivery of Bleomycin after PCI with the photosensitizer Fimaporfin. A systematic variation of Bleomycin and Fimaporfin concentrations and light irradiation led to the pronounced cell death of HNSCC cells. After optimization, the same level of tumor cell death of 75% was reached with a 20-fold lower Bleomycin concentration. This would allow treatment of HNSCC with high local tumor cell death and reduce the side effects of Bleomycin, e.g., lung fibrosis, at the same time. This demonstrates the increased efficacy of the anti-tumor medication Bleomycin in combination with PCI.

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“…Photochemical internalization (PCI) is an efficient strategy for the endosomal escape of the delivered molecules that uses light and photosensitizers . PCI‐mediated delivery of macromolecules like proteins and nucleic acids in vitro or in vivo has been widely used and discussed by many research groups . PCI efficacy relies on an understanding of the endosomal escape mechanism involving the actions of photosensitizers and carrier systems used.…”

Section: Introductionmentioning

confidence: 99%

Relation of Photochemical Internalization to Heat, pH and Ca²⁺ Ions

Soe

Nanjo

Watanabe

et al. 2019

Photochem & Photobiology

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The inefficient endosomal escape of drugs or macromolecules is a major obstacle to achieving successful delivery to therapeutic targets. An efficient approach to circumvent this barrier is photochemical internalization (PCI), which uses light and photosensitizers for endosomal escape of the delivered macromolecules. The PCI mechanism is related to photogenerated singlet oxygen, but the mechanism is still unclear. In this study, we examined the relation of PCI to heat, pH and Ca2+ ions using cell penetrating peptide (CPP)‐cargo‐photosensitizer (Alexa546 or Alexa633) conjugates. A cell temperature changing experiment demonstrated that heat (thermal mechanism) does not significantly contribute to the photoinduced endosomal escape. Inhibition of V‐ATPase proton pump activity and endosomal pH upregulation indicated that PCI‐mediated endosomal escape needs endosomal acidification prior to photoirradiation. Imaging of the CPP‐cargo‐photosensitizer and Ca2+ ions during photostimulation showed that intracellular calcium increase is not the cause of the endosomal escape of the complex. The increment is mainly due to Ca2+ influx. These findings show the importance of extra‐ and intracellular milieu conditions in the PCI mechanism and enrich our understanding of PCI‐related changes in cell.

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Photochemical internalization (PCI) of bleomycin is equally effective in two dissimilar leiomyosarcoma xenografts in athymic mice

Cited by 4 publications

References 40 publications

Proteomic analysis reveals mechanisms underlying increased efficacy of bleomycin by photochemical internalization in bladder cancer cells

Proteomic analysis reveals mechanisms underlying increased efficacy of bleomycin by photochemical internalization in bladder cancer cells

Photochemical Internalization with Fimaporfin: Enhanced Bleomycin Treatment for Head and Neck Cancer

Relation of Photochemical Internalization to Heat, pH and Ca²⁺ Ions

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Photochemical internalization (PCI) of bleomycin is equally effective in two dissimilar leiomyosarcoma xenografts in athymic mice

Cited by 4 publications

References 40 publications

Proteomic analysis reveals mechanisms underlying increased efficacy of bleomycin by photochemical internalization in bladder cancer cells

Proteomic analysis reveals mechanisms underlying increased efficacy of bleomycin by photochemical internalization in bladder cancer cells

Photochemical Internalization with Fimaporfin: Enhanced Bleomycin Treatment for Head and Neck Cancer

Relation of Photochemical Internalization to Heat, pH and Ca2+ Ions

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Relation of Photochemical Internalization to Heat, pH and Ca²⁺ Ions