Actively targeted photodynamic therapy in multicellular colorectal cancer spheroids via functionalised gold nanoparticles

Abstract

Photodynamic therapy (PDT) holds great potential to overcome limitations associated with common colorectal cancer (CRC) treatment approaches. Targeted photosensitiser (PS) delivery systems using nanoparticles (NPs) with targeting moieties are continually being designed, which are aimed at enhancing PS efficacy in CRC PDT. However, the optimisation of targeted PS delivery systems in most, in vitro PDT studies has been conducted on two dimensional (2D) monolayers cell cultures. In our present study, we developed a nano PS delivery system for in vitro cultured human colorectal three-dimensional multicellular spheroids (3D MCTS). PEGylated gold nanoparticles (PEG-AuNPs) were prepared and attached to ZnPcS₄PS and further functionalised with specific CRC targeting anti-Guanylate Cyclase monoclonal antibodies(mAb). The ZnPcS₄-AuNP-Anti-GCC Ab (BNC) nanoconjugates were successfully synthesised and their photodynamic effect investigated following exposure to laser irradiation and demonstrated enhanced anticancer effects in Caco-2 cells cultivated as 3D MCTS spheroids. Our findings suggest that targeted BNC nanoconjugates can improve the efficacy of PDT and highlight the potential of 3D MCTS tumour model for evaluating of targeted PDT.

Keywords:

• Colorectal cancer
• photodynamic therapy
• nanoparticles
• photosensitiser
• three-dimensional (3D) culture models

Acknowledgements

The authors gratefully acknowledge the support from the Organization for Women in Science for the Developing World (OWSD) and the Swedish International Development Cooperation Agency (SIDA) for the fellowship received by N.W.N.S.

Authors contributions

Conceptualisation, N.W.N.S and H.A; Methodology, N.W.N.S; Investigation N.W.N.S; Writing original draft preparation, N.W.N.S; Writing-review and editing, N.W.N.S, H.A; Supervision, H.A.; Funding acquisition. H.A.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the results are available in this article. Additional data are available from the corresponding author, upon reasonable request.

Additional information

Funding

This research is funded by the South African Research Chairs Initiative of the Department of Science and Technology and the National Research Foundation of South Africa, grant number 98337. The authors sincerely thank the Laser Research Centre, the University of Johannesburg, the National Laser Centre, and the National Research Foundation-South African Research Chairs Initiative (NRF-SARCHI) for their financial grant support.