Photodynamic therapy

Materials science

Cancer research

Biochemistry

Hyperthermia

Radiation therapy

Tumor hypoxia

Biomarker

Singlet oxygen

Nanotechnology

Organic chemistry

Oxygen

Photothermal therapy

Tumor microenvironment

Tumor cells

Internal medicine

Medicine

Chemistry

Cancer

Angewandte Chemie International Edition

Activatable phototheranostics holds promise for precision cancer treatment owing to the “turn‐on” signals and therapeutic effects. However, most activatable phototheranostic probes only possess photodynamic therapy (PDT) or photothermal therapy (PTT), which suffer from poor therapeutic efficacy due to deficient cellular oxygen and complex tumor microenvironment. We herein report a dual‐locked activatable phototheranostic probe that activates near‐infrared fluorescence (NIRF) signals in tumor, triggers PDT in response to a tumor‐periphery biomarker, and switches from PDT to PTT upon detecting a tumor‐core‐hypoxia biomarker. This PDT‐PTT auto‐regulated probe exhibits complete tumor ablation under the photoirradiation of a single laser source by producing cytotoxic singlet oxygen at the tumor periphery and generating hyperthermia at tumor‐core where is too hypoxic for PDT. This dual‐locked probe represents a promising molecular design approach toward precise cancer phototheranostics.

A Dual‐Locked Activatable Phototheranostic Probe for Biomarker‐Regulated Photodynamic and Photothermal Cancer Therapy