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Could clinical photochemical internalisation be optimised to avoid neuronal toxicity?

Caitriona O'Rourke1, Colin Hopper2, Alexander J MacRobert3

  • 1Division of Surgery & Interventional Science, University College London, London, UK; Department of Biomaterials & Tissue Engineering, UCL Eastman Dental Institute, University College London, London, UK.

International Journal of Pharmaceutics
|June 6, 2017
PubMed
Summary

Photochemical Internalisation (PCI) uses light-activated drugs to release cancer treatments. This study found PCI can treat tumors near nerves without causing significant nerve damage, making it a promising cancer therapy.

Keywords:
3D culture modelsBleomycinBleomycin (PubChem CID: 5360373)Meso-tetraphenylporphine (PubChem CID: 70186)Nervous systemPhotochemical InternalisationPhotosensitisersTetraphenylchlorin disulfonate (PubChem CID: 44177671)

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Area of Science:

  • Biomedical Engineering
  • Oncology
  • Neuroscience

Background:

  • Photochemical Internalisation (PCI) is an emerging drug delivery technology for cancer treatment.
  • PCI utilizes low-dose photodynamic therapy (PDT) to rupture endo/lysosomes, enabling intracellular drug release.
  • Assessing potential neurotoxicity is crucial for PCI applications near nervous system tissue.

Purpose of the Study:

  • To evaluate the safety and efficacy of Photochemical Internalisation (PCI) on nerve cells.
  • To determine the potential for nerve damage when treating cancers adjacent to nervous system tissue using PCI.
  • To assess the sensitivity of dorsal root ganglion (DRG) neurons and associated glia to PCI treatment.

Main Methods:

  • Utilized a 3D co-culture system with dorsal root ganglion (DRG) neurons and satellite glia.
  • Incubated cells with photosensitisers (TPPS2a or TPCS2a) and Bleomycin for PCI treatment.
  • Exposed co-cultures to light activation to induce PCI and assessed cell viability and neurite length.

Main Results:

  • Cancer cell line PCI30 and satellite glia showed higher sensitivity to PCI than neurons and mixed glial cells.
  • Neurite length in neurons was affected by PCI treatment, indicating some impact on nerve structure.
  • Neurons survived PCI treatment under conditions lethal to tumor cells, suggesting a favorable safety profile.

Conclusions:

  • PCI demonstrates potential for treating cancers within or adjacent to nervous system tissue.
  • The technology appears to spare neurons while effectively targeting cancer cells.
  • Further development of PCI is warranted, considering its neuroprotective potential in cancer therapy.