Suppression of tumour growth from transplanted astrocytoma cells transfected with luciferase in mice by bioluminescence mediated, systemic, photodynamic therapy.

Bioluminescence mediated Photodynamic Therapy (bPDT) Grade 4 astrocytoma cells Subcutaneous and Intracranial tumour growth suppression Transfection of cells with luciferase mTHPC

Journal

Photodiagnosis and photodynamic therapy
ISSN: 1873-1597
Titre abrégé: Photodiagnosis Photodyn Ther
Pays: Netherlands
ID NLM: 101226123

Informations de publication

Date de publication:
13 Dec 2023
Historique:
received: 19 10 2023
revised: 27 11 2023
accepted: 01 12 2023
medline: 16 12 2023
pubmed: 16 12 2023
entrez: 15 12 2023
Statut: aheadofprint

Résumé

Grade 4 astrocytomas are usually incurable due to their diffusely infiltrative nature. Photodynamic therapy (PDT) is a promising therapeutic option, but external light delivery is impractical when cancer cells infiltrate unknown areas of normal brain. Hence the search for endogenous sources to generate light at cancer cells. In vitro, astrocytoma cells, transfected with firefly luciferase, can be killed by bioluminescence-mediated PDT (bPDT). This study asks if bPDT can suppress tumour growth in vivo, when all components of treatment are administered systemically. Transfected astrocytoma cells were injected subcutaneously or intra-cranially in athymic CD1 nu/nu mice. bPDT required ip bolus of mTHPC (photosensitiser) and delivery of the D-luciferin substrate over 7 days via an implanted osmotic pump. Control animals had no treatment, photosensitiser only or D-luciferin only. For subcutaneous tumours, size and BLI (light emitted after D-luciferin bolus) were measured before and every 2 days after PDT. For intracranial tumours, monitoring was weekly BLI. For subcutaneous tumours, there was significant suppression of the tumour growth rate (P<0.05), and absolute tumour size (P<0.01) after bPDT. Proliferation of subcutaneous and intracranial tumours (monitored by BrdU uptake) was significantly reduced in treated mice. (P<0.001) CONCLUSIONS: This study reports bPDT suppression of tumour growth from luciferase transfected astrocytoma cells with all components of treatment given systemically, as required for effective management of recurrent astrocytomas in unknown sites. However, research on systemic bPDT is needed to establish whether effects on non-transfected tumours can be achieved without any unacceptable effects on normal tissues.

Sections du résumé

BACKGROUND BACKGROUND
Grade 4 astrocytomas are usually incurable due to their diffusely infiltrative nature. Photodynamic therapy (PDT) is a promising therapeutic option, but external light delivery is impractical when cancer cells infiltrate unknown areas of normal brain. Hence the search for endogenous sources to generate light at cancer cells. In vitro, astrocytoma cells, transfected with firefly luciferase, can be killed by bioluminescence-mediated PDT (bPDT). This study asks if bPDT can suppress tumour growth in vivo, when all components of treatment are administered systemically.
METHODS METHODS
Transfected astrocytoma cells were injected subcutaneously or intra-cranially in athymic CD1 nu/nu mice. bPDT required ip bolus of mTHPC (photosensitiser) and delivery of the D-luciferin substrate over 7 days via an implanted osmotic pump. Control animals had no treatment, photosensitiser only or D-luciferin only. For subcutaneous tumours, size and BLI (light emitted after D-luciferin bolus) were measured before and every 2 days after PDT. For intracranial tumours, monitoring was weekly BLI.
RESULTS RESULTS
For subcutaneous tumours, there was significant suppression of the tumour growth rate (P<0.05), and absolute tumour size (P<0.01) after bPDT. Proliferation of subcutaneous and intracranial tumours (monitored by BrdU uptake) was significantly reduced in treated mice. (P<0.001) CONCLUSIONS: This study reports bPDT suppression of tumour growth from luciferase transfected astrocytoma cells with all components of treatment given systemically, as required for effective management of recurrent astrocytomas in unknown sites. However, research on systemic bPDT is needed to establish whether effects on non-transfected tumours can be achieved without any unacceptable effects on normal tissues.

Identifiants

DOI: 10.1016/j.pdpdt.2023.103923 PMID: 38101502
pubmed: 38101502
pii: S1572-1000(23)00650-6
doi: 10.1016/j.pdpdt.2023.103923
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

103923

Informations de copyright

Copyright © 2023. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest None

Auteurs

Jane Ng (J)

UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG; National Medical Laser Centre (now Department of Targeted Intervention, Division of Surgery and Interventional Science), University College London, Charles Bell House 43-45 Foley Street, London W1W 7TS. Electronic address: janeswng@yahoo.co.uk.

Nico Henriquez (N)

UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG. Electronic address: henriqnv@gmail.com.

Neil Kitchen (N)

Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, UCLH NHS Trust, Queen Square, London WC1 3BG, UK. Electronic address: neilkitchen@nhs.net.

Norman Williams (N)

Division of Surgery & Interventional Science, University College London, Charles Bell House, 43-45 Foley Street London W1W 7TS UK. Electronic address: norman.williams@ucl.ac.uk.

Marco Novelli (M)

Department of Cellular Pathology, University College Hospital, London, 60 Whitfield Street, London W1T 4EU. Electronic address: m.novelli@ucl.ac.uk.

Dahmane Oukrif (D)

Department of Cellular Pathology, University College Hospital, London, 60 Whitfield Street, London W1T 4EU. Electronic address: dahmane.oukrif@ucl.ac.uk.

Alexander MacRobert (A)

National Medical Laser Centre (now Department of Targeted Intervention, Division of Surgery and Interventional Science), University College London, Charles Bell House 43-45 Foley Street, London W1W 7TS. Electronic address: a.macrobert@ucl.ac.uk.

Stephen Bown (S)

National Medical Laser Centre (now Department of Targeted Intervention, Division of Surgery and Interventional Science), University College London, Charles Bell House 43-45 Foley Street, London W1W 7TS. Electronic address: s.bown@ucl.ac.uk.

Classifications MeSH