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Tumour associated vasculature-on-a-chip for the evaluation of microbubble-mediated delivery of targeted liposomes.
Bourn, Matthew D; Mohajerani, Safoura Zahed; Mavria, Georgia; Ingram, Nicola; Coletta, P Louise; Evans, Stephen D; Peyman, Sally A.
Afiliación
  • Bourn MD; School of Physics and Astronomy, University of Leeds, Leeds, LS2 9JT, UK. s.peyman@leeds.ac.uk.
  • Mohajerani SZ; Leeds Institute for Medical Research, Wellcome Trust Brenner Building, St James' University Hospital, Leeds, LS9 7TF, UK.
  • Mavria G; Leeds Institute for Medical Research, Wellcome Trust Brenner Building, St James' University Hospital, Leeds, LS9 7TF, UK.
  • Ingram N; Leeds Institute for Medical Research, Wellcome Trust Brenner Building, St James' University Hospital, Leeds, LS9 7TF, UK.
  • Coletta PL; Leeds Institute for Medical Research, Wellcome Trust Brenner Building, St James' University Hospital, Leeds, LS9 7TF, UK.
  • Evans SD; Leeds Institute for Medical Research, Wellcome Trust Brenner Building, St James' University Hospital, Leeds, LS9 7TF, UK.
  • Peyman SA; School of Physics and Astronomy, University of Leeds, Leeds, LS2 9JT, UK. s.peyman@leeds.ac.uk.
Lab Chip ; 23(6): 1674-1693, 2023 03 14.
Article en En | MEDLINE | ID: mdl-36779251
The vascular system is the primary route for the delivery of therapeutic drugs throughout the body and is an important barrier at the region of disease interest, such as a solid tumour. The development of complex 3D tumour cultures has progressed significantly in recent years however, the generation of perfusable vascularised tumour models still presents many challenges. This study presents a microfluidic-based vasculature system that can be induced to display properties of tumour-associated blood vessels without direct incorporation of tumour cells. Conditioning healthy endothelial-fibroblast cell vasculature co-cultures with media taken from tumour cell cultures was found to result in the formation of disorganised, tortuous networks which display characteristics consistent with those of tumour-associated vasculature. Integrin αvß3, a cell adhesion receptor associated with angiogenesis, was found to be upregulated in vasculature co-cultures conditioned with tumour cell media (TCM) - consistent with the reported αvß3 expression pattern in angiogenic tumour vasculature in vivo. Increased accumulation of liposomes (LSs) conjugated to antibodies against αvß3 was observed in TCM networks compared to non-conditioned networks, indicating αvß3 may be a potential target for the delivery of drugs specifically to tumour vasculature. Furthermore, the use of microbubbles (MBs) and ultrasound (US) to further enhance the delivery of LSs to TCM-conditioned vasculature was investigated. Quantification of fluorescent LS accumulation post-perfusion of the vascular network showed 3-fold increased accumulation with the use of MBs and US, suggesting that targeted LS delivery could be further improved with the use of locally administered MBs and US.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microburbujas / Liposomas Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Lab Chip Asunto de la revista: BIOTECNOLOGIA / QUIMICA Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microburbujas / Liposomas Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Lab Chip Asunto de la revista: BIOTECNOLOGIA / QUIMICA Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido