In silico analysis of hypoxia activated prodrugs in combination with anti angiogenic therapy through nanocell delivery.
Journal
PLoS computational biology
ISSN: 1553-7358
Titre abrégé: PLoS Comput Biol
Pays: United States
ID NLM: 101238922
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
04
12
2019
accepted:
05
05
2020
revised:
09
06
2020
pubmed:
29
5
2020
medline:
29
8
2020
entrez:
29
5
2020
Statut:
epublish
Résumé
Tumour hypoxia is a well-studied phenomenon with implications in cancer progression, treatment resistance, and patient survival. While a clear adverse prognosticator, hypoxia is also a theoretically ideal target for guided drug delivery. This idea has lead to the development of hypoxia-activated prodrugs (HAPs): a class of chemotherapeutics which remain inactive in the body until metabolized within hypoxic regions. In theory, these drugs have the potential for increased tumour selectivity and have therefore been the focus of numerous preclinical studies. Unfortunately, HAPs have had mixed results in clinical trials, necessitating further study in order to harness their therapeutic potential. One possible avenue for the improvement of HAPs is through the selective application of anti angiogenic agents (AAs) to improve drug delivery. Such techniques have been used in combination with other conventional chemotherapeutics to great effect in many studies. A further benefit is theoretically achieved through nanocell administration of the combination, though this idea has not been the subject of any experimental or mathematical studies to date. In the following, a mathematical model is outlined and used to compare the predicted efficacies of separate vs. nanocell administration for AAs and HAPs in tumours. The model is experimentally motivated, both in mathematical form and parameter values. Preliminary results of the model are highlighted throughout which qualitatively agree with existing experimental evidence. The novel prediction of our model is an improvement in the efficacy of AA/HAP combination therapies when administered through nanocells as opposed to separately. While this study specifically models treatment on glioblastoma, similar analyses could be performed for other vascularized tumours, making the results potentially applicable to a range of tumour types.
Identifiants
pubmed: 32463836
doi: 10.1371/journal.pcbi.1007926
pii: PCOMPBIOL-D-19-02120
pmc: PMC7282674
doi:
Substances chimiques
Angiogenesis Inhibitors
0
Prodrugs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007926Subventions
Organisme : CIHR
Pays : Canada
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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