O-P03 A composite polymeric nanoparticle as a sensitiser for sonodynamic therapy (SDT)-based treatment of pancreatic cancer
Sian Farrell, Heather Nesbitt, Laura Mairs, Nikolitsa Nomikou, Bridgeen Callan, John F. Callan, Anthony P McHale
School of Pharm. & Pharmaceut. Sc.
Abstract Background Pancreatic cancer remains one of the most recalcitrant forms of cancer with poor prognosis and limited treatment options. SDT is a novel, targeted approach to the treatment of solid tumours. Based on the generation of cytotoxic reactive oxygen species (ROS) following the exposure of a sonosensitiser to ultrasound, the approach is designed to extracorporeally target less accessible lesions. Here we describe the production of a poly(lactic-co-glycolic acid) (PLGA), polyethyleneimine (PEI), Rose Bengal (RB) and indocyanine green (ICG) containing composite nanoparticles and describe their use in SDT-mediated treatment of pancreatic cancer using both in vitro and in vivo target models. Methods Nanoparticles were prepared using an oil in water emulsion and solvent diffusion-based approach. These were designated RB-ICGNP. In vitro SDT treatment consisted of exposing BxPC3 (human PDAC cells), T110029 (murine PDAC cells) or hPSC (immortalised human pancreatic stellate cells) to RB-ICGNP and subsequently treating with ultrasound for 30 s at a frequency of 1 MHz, a power density of 3.0 W/cm2 (SATP) using a duty cycle of 50% at a pulse repetition frequency of 100 Hz. For in vivo studies, BxPC3 (xenograft) and T110029 (syngeneic) tumours were treated with a power density of 3.5 W/cm2 ultrasound for 3.5 min. Results Conclusions Using in vitro and in vivo (human xenograft and murine syngeneic) models of pancreatic cancer, RB-ICGNP composite nanoparticles may be employed as a sensitiser for SDT-based treatment of pancreatic cancer. Since pancreatic stellate cells were more sensitive to SDT, the latter may have an impact on tumour stroma. Staining of residual tumour tissues from SDT-treated animals for connective tissue (stroma) confirmed the latter. Since tumour stroma presents a significant challenge to treatment of pancreatic cancer and represents a negative prognostic marker, the impact delivered by SDT may be exploited to potentiate alternative therapeutic approaches.
British Journal of Surgery
Supplement_9
https://doi.org/10.1093/bjs/znab429.044
10.1093/bjs/znab429.044
Dive into the research topics of 'O-P03 A composite polymeric nanoparticle as a sensitiser for sonodynamic therapy (SDT)-based treatment of pancreatic cancer'. Together they form a unique fingerprint.
Pancreatic Neoplasms Medicine & Life Sciences 100%
Rose Bengal Medicine & Life Sciences 45%
Pancreatic Stellate Cells Medicine & Life Sciences 25%
S-acetylthiorphan Medicine & Life Sciences 17%
Heterografts Medicine & Life Sciences 14%
Farrell, S., Nesbitt, H., Mairs, L., Nomikou, N., Callan, B., Callan, J. F., & McHale, A. P. (2021). O-P03 A composite polymeric nanoparticle as a sensitiser for sonodynamic therapy (SDT)-based treatment of pancreatic cancer. British Journal of Surgery, 108(Supplement_9), ix17. https://doi.org/10.1093/bjs/znab429.044
Farrell, Sian ; Nesbitt, Heather ; Mairs, Laura ; Nomikou, Nikolitsa ; Callan, Bridgeen ; Callan, John F. ; McHale, Anthony P. / O-P03 A composite polymeric nanoparticle as a sensitiser for sonodynamic therapy (SDT)-based treatment of pancreatic cancer. In: British Journal of Surgery. 2021 ; Vol. 108, No. Supplement_9. pp. ix17.
@article{47572ccf323a48b4b14435bd817eee69,
title = "O-P03 A composite polymeric nanoparticle as a sensitiser for sonodynamic therapy (SDT)-based treatment of pancreatic cancer",
abstract = "Abstract Background Pancreatic cancer remains one of the most recalcitrant forms of cancer with poor prognosis and limited treatment options. SDT is a novel, targeted approach to the treatment of solid tumours. Based on the generation of cytotoxic reactive oxygen species (ROS) following the exposure of a sonosensitiser to ultrasound, the approach is designed to extracorporeally target less accessible lesions. Here we describe the production of a poly(lactic-co-glycolic acid) (PLGA), polyethyleneimine (PEI), Rose Bengal (RB) and indocyanine green (ICG) containing composite nanoparticles and describe their use in SDT-mediated treatment of pancreatic cancer using both in vitro and in vivo target models. Methods Nanoparticles were prepared using an oil in water emulsion and solvent diffusion-based approach. These were designated RB-ICGNP. In vitro SDT treatment consisted of exposing BxPC3 (human PDAC cells), T110029 (murine PDAC cells) or hPSC (immortalised human pancreatic stellate cells) to RB-ICGNP and subsequently treating with ultrasound for 30 s at a frequency of 1 MHz, a power density of 3.0 W/cm2 (SATP) using a duty cycle of 50% at a pulse repetition frequency of 100 Hz. For in vivo studies, BxPC3 (xenograft) and T110029 (syngeneic) tumours were treated with a power density of 3.5 W/cm2 ultrasound for 3.5 min. Results Conclusions Using in vitro and in vivo (human xenograft and murine syngeneic) models of pancreatic cancer, RB-ICGNP composite nanoparticles may be employed as a sensitiser for SDT-based treatment of pancreatic cancer. Since pancreatic stellate cells were more sensitive to SDT, the latter may have an impact on tumour stroma. Staining of residual tumour tissues from SDT-treated animals for connective tissue (stroma) confirmed the latter. Since tumour stroma presents a significant challenge to treatment of pancreatic cancer and represents a negative prognostic marker, the impact delivered by SDT may be exploited to potentiate alternative therapeutic approaches.",
keywords = "Surgery",
author = "Sian Farrell and Heather Nesbitt and Laura Mairs and Nikolitsa Nomikou and Bridgeen Callan and Callan, {John F.} and McHale, {Anthony P}",
doi = "10.1093/bjs/znab429.044",
pages = "ix17",
journal = "British Journal of Surgery",
number = "Supplement_9",
Farrell, S, Nesbitt, H, Mairs, L, Nomikou, N, Callan, B, Callan, JF & McHale, AP 2021, 'O-P03 A composite polymeric nanoparticle as a sensitiser for sonodynamic therapy (SDT)-based treatment of pancreatic cancer', British Journal of Surgery, vol. 108, no. Supplement_9, pp. ix17. https://doi.org/10.1093/bjs/znab429.044
O-P03 A composite polymeric nanoparticle as a sensitiser for sonodynamic therapy (SDT)-based treatment of pancreatic cancer. / Farrell, Sian; Nesbitt, Heather; Mairs, Laura; Nomikou, Nikolitsa; Callan, Bridgeen; Callan, John F.; McHale, Anthony P.
In: British Journal of Surgery, Vol. 108, No. Supplement_9, 15.12.2021, p. ix17.
T1 - O-P03 A composite polymeric nanoparticle as a sensitiser for sonodynamic therapy (SDT)-based treatment of pancreatic cancer
AU - Farrell, Sian
AU - Nesbitt, Heather
AU - Mairs, Laura
AU - Nomikou, Nikolitsa
AU - Callan, Bridgeen
AU - Callan, John F.
AU - McHale, Anthony P
N2 - Abstract Background Pancreatic cancer remains one of the most recalcitrant forms of cancer with poor prognosis and limited treatment options. SDT is a novel, targeted approach to the treatment of solid tumours. Based on the generation of cytotoxic reactive oxygen species (ROS) following the exposure of a sonosensitiser to ultrasound, the approach is designed to extracorporeally target less accessible lesions. Here we describe the production of a poly(lactic-co-glycolic acid) (PLGA), polyethyleneimine (PEI), Rose Bengal (RB) and indocyanine green (ICG) containing composite nanoparticles and describe their use in SDT-mediated treatment of pancreatic cancer using both in vitro and in vivo target models. Methods Nanoparticles were prepared using an oil in water emulsion and solvent diffusion-based approach. These were designated RB-ICGNP. In vitro SDT treatment consisted of exposing BxPC3 (human PDAC cells), T110029 (murine PDAC cells) or hPSC (immortalised human pancreatic stellate cells) to RB-ICGNP and subsequently treating with ultrasound for 30 s at a frequency of 1 MHz, a power density of 3.0 W/cm2 (SATP) using a duty cycle of 50% at a pulse repetition frequency of 100 Hz. For in vivo studies, BxPC3 (xenograft) and T110029 (syngeneic) tumours were treated with a power density of 3.5 W/cm2 ultrasound for 3.5 min. Results Conclusions Using in vitro and in vivo (human xenograft and murine syngeneic) models of pancreatic cancer, RB-ICGNP composite nanoparticles may be employed as a sensitiser for SDT-based treatment of pancreatic cancer. Since pancreatic stellate cells were more sensitive to SDT, the latter may have an impact on tumour stroma. Staining of residual tumour tissues from SDT-treated animals for connective tissue (stroma) confirmed the latter. Since tumour stroma presents a significant challenge to treatment of pancreatic cancer and represents a negative prognostic marker, the impact delivered by SDT may be exploited to potentiate alternative therapeutic approaches.
AB - Abstract Background Pancreatic cancer remains one of the most recalcitrant forms of cancer with poor prognosis and limited treatment options. SDT is a novel, targeted approach to the treatment of solid tumours. Based on the generation of cytotoxic reactive oxygen species (ROS) following the exposure of a sonosensitiser to ultrasound, the approach is designed to extracorporeally target less accessible lesions. Here we describe the production of a poly(lactic-co-glycolic acid) (PLGA), polyethyleneimine (PEI), Rose Bengal (RB) and indocyanine green (ICG) containing composite nanoparticles and describe their use in SDT-mediated treatment of pancreatic cancer using both in vitro and in vivo target models. Methods Nanoparticles were prepared using an oil in water emulsion and solvent diffusion-based approach. These were designated RB-ICGNP. In vitro SDT treatment consisted of exposing BxPC3 (human PDAC cells), T110029 (murine PDAC cells) or hPSC (immortalised human pancreatic stellate cells) to RB-ICGNP and subsequently treating with ultrasound for 30 s at a frequency of 1 MHz, a power density of 3.0 W/cm2 (SATP) using a duty cycle of 50% at a pulse repetition frequency of 100 Hz. For in vivo studies, BxPC3 (xenograft) and T110029 (syngeneic) tumours were treated with a power density of 3.5 W/cm2 ultrasound for 3.5 min. Results Conclusions Using in vitro and in vivo (human xenograft and murine syngeneic) models of pancreatic cancer, RB-ICGNP composite nanoparticles may be employed as a sensitiser for SDT-based treatment of pancreatic cancer. Since pancreatic stellate cells were more sensitive to SDT, the latter may have an impact on tumour stroma. Staining of residual tumour tissues from SDT-treated animals for connective tissue (stroma) confirmed the latter. Since tumour stroma presents a significant challenge to treatment of pancreatic cancer and represents a negative prognostic marker, the impact delivered by SDT may be exploited to potentiate alternative therapeutic approaches.
KW - Surgery
U2 - 10.1093/bjs/znab429.044
DO - 10.1093/bjs/znab429.044
SP - ix17
JO - British Journal of Surgery
JF - British Journal of Surgery
IS - Supplement_9
Farrell S, Nesbitt H, Mairs L, Nomikou N, Callan B, Callan JF et al. O-P03 A composite polymeric nanoparticle as a sensitiser for sonodynamic therapy (SDT)-based treatment of pancreatic cancer. British Journal of Surgery. 2021 Dec 15;108(Supplement_9):ix17. https://doi.org/10.1093/bjs/znab429.044