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).