In situ sonoporation to enhance the tumour uptake of silicon phthalocyanine and improve PDT effectiveness in a triple negative breast cancer murine model

The effectiveness of photodynamic therapy (PDT) has been well demonstrated in vitro, but in vivo studies have only shown a delay in tumour growth. Tumour recurrence is often reported in clinical trials and is usually associated with limited tumour uptake of the photosensitiser (PS). In this study, sonoporation (SNP) is utilised as a physical targeting tool to enhance the uptake of an untargeted PS in cells and tumour tissues. Using a chemometric approach, we identified the optimal sonoporation stimulus to maximise uptake and cell viability (frequency 1.05 MHz, tON (percentage of positive signal in a single pulse): 50 %, DC: 90 %, burst: 1 s, sonoporation time 1 min). We achieved a viability of 83.9 % ± 10.3, and an uptake in live cells of 53.1 % ± 6.6. The combination of sonoporation and photodynamic therapy resulted in a significant reduction in cell viability. In a triple-negative breast cancer model, sonoporation combined with photodynamic therapy significantly inhibited tumour growth. For the first time, our results highlight the potential of sonoporation as a non-invasive method to increase the intratumour uptake of photosensitisers, offering a promising strategy to improve PDT efficacy.