Review of three-dimensional spheroid culture models of gynecological cancers for photodynamic therapy research

Photodynamic therapy (PDT) is a specific cancer treatment with minimal side effects. However, it remains challenging to apply PDT clinically, partially due to the difficulty of translating research findings to clinical settings as the conventional 2D cell models used for in vitro research are accepted as less physiologically relevant to a solid tumour. 3D spheroids offer a better model for testing PDT mechanisms and efficacy, particularly on photosensitizer uptake, cellular and subcellular distribution and interaction with cellular oxygen consumption. 3D spheroids are usually generated by scaffold-free and scaffold-based methods and are accepted as physiologically relevant models for PDT anticancer research. Scaffold-free methods offer researchers advantages including high efficiency, reproducible, and controlled microenvironment. While the scaffold-based methods offer an extracellular matrix-like 3D scaffold with the necessary architecture and chemical mediators to support the spheroid formation, the natural scaffold used may limit its usage because of low reproducibility due to patch-to-patch variation. Many studies show that the 3D spheroids do offer advantages to gynceologcial cancer PDT investigation. This article will provide a review of the applications of 3D spheroid culture models for the PDT research of gynaecological cancers.