O-P03 A composite polymeric nanoparticle as a sensitiser for sonodynamic therapy (SDT)-based treatment of pancreatic cancer. (16th December 2021)

• Record Type: Journal Article
• Authors: Farrell, Sian; Nesbitt, Heather; Mairs, Laura; Nomikou, Nikolitsa; Callan, Bridgeen; Callan, John F.; McHale, Anthony P.
• Is Part Of: British journal of surgery. Volume 108:Supplement 9(2021)
• Publication Date: 2021-12-16
• Subjects: Surgery -- Periodicals; 617.005
• DOI: 10.1093/bjs/znab429.044
• Languages: English
• ISSNs: 0007-1323

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/cm 2 (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/cm 2 ultrasound for 3.5 min. Results: Of the three cell lines treated with RB-ICGNP-mediated SDT, the pancreatic stellate cell line was the most sensitive. This suggested that SDT may play a role in reducing tumour stroma. By exploiting the ICG in the nanoparticles, realtime nIR fluorescene imaging of tumour-bearing animals following IV administration of RB-ICGNPs, demonstrated tumour uptake of nanoparticles. Both human xenograft and syngeneic preclinical models of pancreatic cancer exhibited significant responses to RB-ICGNP-mediated SDT. Histological staining of residual tumour tissues from SDT-treated animals with Sirius Red (connective tissue) demonstrated reduced stroma when compared with untreated tumours. 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.