Near-infrared-activated upconversion nanoprobes for sensitive endogenous Zn²⁺ detection and selective on-demand photodynamic therapy

As a light-activated noninvasive cancer treatment paradigm, photodynamic therapy (PDT) has attracted extensive attention because of its high treatment efficacy and low side effects. Especially, spatiotemporal control of singlet oxygen (¹O₂) release is highly desirable for realizing on-demand PDT, which, however, still remains a huge challenge. To address this issue, a novel switchable near-infrared (NIR)-responsive upconversion nanoprobe has been designed and successfully applied for controlled PDT that can be optically activated by tumor-associated disruption of labile Zn²⁺ (denoted as Zn²⁺ hereafter) homeostasis stimuli. Upon NIR irradiation, this theranostic probe can not only quantitatively detect the intracellular endogenous Zn²⁺ in situ but also selectively generate a great deal of cytotoxic reactive oxygen species (ROS) for efficiently killing breast cancer cells under the activation of excessive endogenous Zn²⁺, so as to maximally avoid adverse damage to normal cells. This study aims to propose a new tumor-specific PDT paradigm and, more importantly, provide a new avenue of thought for efficient cancer theranostics based on our designed highly sensitive upconversion nanoprobes. (Figure Presented).