Dual-step irradiation strategy to sequentially destroy singlet oxygen-responsive polymeric micelles and boost photodynamic cancer therapy.

Nanotechnology provides a powerful tool to overcome many disadvantages of small-molecule photosensitizers for photodynamic cancer therapy, such as hydrophobicity, rapid blood clearance, low accumulation in tumor tissue and low cell penetration, etc. The occurrence of quench in photosensitizer-loaded nanoparticle greatly downregulates the ability to generate singlet oxygen with light irradiation. Stimuli-responsive nanocarriers can improve the efficacy of PDT to a certain extent. However, insufficient release of photosensitizer from either endogenous or exogenous stimuli responsive nanocarriers in the short period of light irradiation restricts full usage of the photosensitizer delivered into cancer cells. We here report a dual-step light irradiation strategy to enhance the efficacy of cancer PDT. Ce6 as a photosensitizer is loaded in singlet oxygen-sensitive micelles (Ce6-M) via self-assembly of amphiphilic polymer mPEG-TK-C. After co-incubation of Ce6-M with cancer cells or i.v. injection of Ce6-M, cancer cells or tumor tissues are irradiated with light for a short time to trigger Ce6 release, and 2 h later, re-irradiated for relatively long time. The sufficient release of Ce6 in the period between twice light irradiation significantly improves the generation of singlet oxygen, leading to more efficient cancer therapeutic effects of dual-step irradiation than that of single-step irradiation for the same total irradiation time.