Photo-activatable prodrug nanoparticles for reactive oxygen species amplification and cooperative cancer therapy

Photodynamic therapy (PDT), as a minimally invasive cancer therapy, demonstrates certain advantages in treating superficial tumors. However, it often faces challenges such as low reactive oxygen species (ROS) generation efficiency and non-targeted distribution of photosensitizers. The combination of chemotherapy and PDT can address the limitations of single modal therapies and improve therapeutic outcomes. In this work, we design a prodrug-based nanomedicine that can achieve photo-activated cascade drug release. Under 660 nm laser irradiation, the generated singlet oxygen can trigger the release of chemotherapeutic agent chlorambucil, cinnamaldehyde and quinone methyl. Chlorambucil can exert anti-tumor effects and cinnamaldehyde can increase intracellular hydrogen peroxide levels, while quinone methyl can consume intracellular glutathione. This process ultimately results in the amplification of ROS signals and further activation of prodrugs. This nanomedicine exhibits the ability to amplify oxidative stress and potent anticancer activity. In vivo experiments show that the nanomedicine can effectively inhibit tumor growth. This work provides a promising mutually beneficial strategy for achieving cooperative cancer therapy.