Acid-responsive singlet oxygen nanodepots

Abstract

The singlet oxygen carrier addresses the challenges of traditional photodynamic therapy (PDT), which relies on the presence of oxygen within solid tumors and struggles with light penetration issues. However, the inability to control the release of singlet oxygen has hindered precise treatment applications. Here, we introduce an acid-responsive singlet oxygen nanodepot (aSOND) designed to overcome this limitation. The aSOND is synthesized using a responsive diblock copolymer system that includes a hydrophilic PEG block and a pH-responsive block with singlet oxygen loading sites. In neutral or alkaline environments, the aSOND releases singlet oxygen slowly, ensuring stability in blood circulation. In contrast, in acidic environments such as the tumor microenvironment or intracellular lysosomes, protonation of the tertiary amine group within the pH responsive block increases the hydration of the polymer, triggering a rapid release of singlet oxygen. This feature enables controlled, tumor-specific release of reactive oxygen species (ROS). The aSOND system effectively implements an “OFF–ON” singlet oxygen therapy, demonstrating high spatiotemporal selectivity and independence from both oxygen supply and external light, offering a promising approach for targeted cancer therapy.