“Click” for precise photodynamic therapy

Abstract

Bioorthogonal chemistry has been a powerful tool in chemical biology. It can facilitate the study of biomolecules in their native environments and enables targeted delivery and controlled release of theranostic agents. Recently, this chemistry has been utilised to advance the development of photodynamic therapy (PDT), which is a promising treatment modality for a range of superficial and localised cancers as well as certain non-cancerous conditions. An array of highly efficient and selective click reactions have been used to introduce tumour-targeting ligands to photosensitisers, deliver photosensitisers to pre-labelled bio-objects and activate the photodynamic activity of photosensitisers via bioorthogonal removal of the quenching unit or in situ synthesis of the photosensitisers. These strategies have been applied to molecular and nano-based photosensitising systems, resulting in targeted delivery and site-specific activation of these photo-responsive therapeutic agents, which can potentially actualise precise PDT. This article aims to introduce the concepts and highlight the recent advances of these innovative “click” approaches.