Chemo-/sonodynamic/photothermal triune therapy in 2D and 3D models of MCF-7 cells using paclitaxel-loaded gold nanoparticles

Abstract

Objective

Breast cancer remains the most prevalent cancer among females globally, with an alarming rise in incidence. Conventional treatments like chemotherapy face several limitations, necessitating innovative approaches. In this study, the efficacy of a novel chemo-/sonodynamic/photothermal triune therapy utilizing paclitaxel-loaded gold nanoparticles (PTX@GNPs) for MCF-7 breast cancer cells treatment was explored.

Methods

PTX@GNPs were synthesized and characterized followed by measurements of 808-nm photothermal conversion efficiency and drug loading capacity. The combined dual therapies of chemotherapy/photothermal therapy (chemo/PTT), chemotherapy/sonodynamic therapy (chemo/SDT), and combined triune therapies of chemotherapy/sonodynamic therapy/photothermal therapy (chemo/SDPTT) and chemotherapy/photothermal therapy/sonodynamic therapy (chemo/PTSDT) of both 2D monolayer and 3D spheroid MCF-7 cells were evaluated using the MTT and resazurin assays, and reactive oxygen species detection. The impact of laser light and ultrasound radiations (light followed by ultrasound and vice versa radiations) was also investigated.

Results

PTX@GNPs exhibited a high loading capacity of 60 % and a photothermal conversion efficiency of 28.7 %. In the 2D culture model, chemo/SDPTT demonstrated superior cytotoxicity and ROS generation, compared to the monotherapies and other dual and triune therapies. In the 3D culture spheroids, while overall cytotoxicity was lower due to slower growth rates and limited oxygen diffusion, chemo/PTSDT again provided the highest efficacy.

Conclusion

The synchronized chemo/PTSDT modality employing PTX@GNPs exhibited significant synergistic effects against both 2D and 3D MCF-7 cell culture models. This approach outperformed free paclitaxel and monotherapies, emphasizing the potential of gold nanoparticles as an effective drug carrier and dual photo/sonosensitizer. Importance of treatment sequence during multimodal cancer therapies for better therapeutic outcomes was highlighted.