Chemiluminescence resonance energy transfer–based nanoparticles for quantum yield–enhanced cancer phototheranostics

Chemiluminescence (CL) has recently gained attention for CL resonance energy transfer (CRET)–mediated photodynamic therapy of cancer. However, the short duration of the CL signal and low quantum yield of the photosensitizer have limited its translational applications. Here, we report CRET-based nanoparticles (CRET-NPs) to achieve quantum yield–enhanced cancer phototheranostics by reinterpreting the hidden nature of CRET. Owing to reactive oxygen species (ROS)–responsive CO2 generation, CRET-NPs were capable of generating a strong and long-lasting photoacoustic signal in the tumor tissue via thermal expansion–induced vaporization. In addition, the CRET phenomenon of the NPs enhanced ROS quantum yield of photosensitizer through both electron transfer for an oxygen-independent type I photochemical reaction and self-illumination for an oxygen-dependent type II photochemical reaction. Consequently, owing to their high ROS quantum yield, CRET-NPs effectively inhibited tumor growth with complete tumor growth inhibition in 60% of cases, even with a single treatment.