Tumor-microenvironment-activatable organic phototheranostic agents for cancer therapy

Tumor microenvironment is a rather unusual circumstances formed during the growth of tumor cells, showing significant differences from normal cells and tissues. Indeed, many biological active species (including enzymes, low pH, and small molecules) in the tumor microenvironment are used as triggered switches in the diagnosis and treatment of cancers. Compared with traditional cancer therapies, optical-based therapies such as photodynamic and photothermal therapies have opened up new avenues for clinical cancer treatment due to their excellent spatio-temporal selectivity, non-resistance, and non-invasiveness, among many other advantages. Intriguingly, in recent years, numerous organic phototheranostic agents based on tumor microenvironmental activation have been prepared, which can be specifically activated in tumor tissues and produce fluorescence to specifically visualize tumor tissues or activate the tumor cell death pathway by reactive oxygen species and heat generation to achieve tumor-specific ablation. In this review, we systematically describe the theranostic mechanism of agents, the design principles of activatable organic phototheranostic agents in response to the tumor microenvironment, their use for tumor-specific imaging and related applications in therapeutics. Additionally, the limitations of current activatable organic phototheranostic agents in clinical applications and the focus of future design directions are discussed.