Immunomodulatory therapies are becoming a paradigm-shifting treatment modality for cancer. Despite promising clinical results, cancer immunotherapy is accompanied with off-tumor toxicity and autoimmune adverse effects. Thus, the development of smarter systems to regulate immune responses with superior spatiotemporal precision and enhanced safety is urgently needed. Here we report an activatable engineered immunodevice that enables remote control over the antitumor immunity in vitro and in vivo with near-infrared (NIR) light. The immunodevice is composed of a rationally designed UV light-activatable immunostimulatory agent and upconversion nanoparticle, which acts as a transducer to shift the light sensitivity of the device to the NIR window. The controlled immune regulation allows the generation of effective immune response within tumor without disturbing immunity elsewhere in the body, thereby maintaining the antitumor efficacy while mitigating systemic toxicity. The present work illustrates the potential of the remote-controlled immunodevice for triggering of immunoactivity at the right time and site.

Fluorescent nanoprobes are indispensable tools to monitor and analyze biological species and dynamic biochemical processes in cells and living bodies. Conventional nanoprobes have limitations in obtaining imaging signals with high precision and resolution because of the interference with biological autofluorescence, off‐target effects, and lack of spatiotemporal control. As a newly developed paradigm, light‐activated nanoprobes, whose imaging and sensing activity can be remotely regulated with light irradiation, show good potential to overcome these limitations. Herein, recent research progress on the design and construction of light‐activated nanoprobes to improve bioimaging and sensing performance in complex biological systems is introduced. First, recent innovative strategies and their underlying mechanisms for light‐controlled imaging are reviewed, including photoswitchable nanoprobes and phototargeted nanosystems. Subsequently, a short highlight is provided on the development of light‐activatable nanoprobes for biosensing, which offer possibilities for the remote control of biorecognition and sensing activity in a precise manner both temporally and spatially. Finally, perspectives and challenges in light‐activated nanoprobes are commented.

DNA-based molecular circuits able to perform complex information processing in biological systems are highly desirable. However, conventional DNA circuits are constitutively always in an ON state and immediately operate when they meet the biomolecular inputs, precluding precise molecular computation at a desired time and in a desired site. In this work, we report a conceptual methodology for the construction of photonic nanocircuits that enable DNA molecular computation in vitro and in vivo with high spatial precision. Upon remote activation by spatially restricted NIRlight input, two types of cancer biomarker inputs can sequentially trigger conformational changes of the DNA circuit through a structure-switching aptamer and toehold-mediated strand exchange, leading to release of a signaling output. Of note, the NIR-light-gated nanocircuit allows for intended control over the specific timing and location of DNA computation, providing spatial and temporal capabilities for multiplexed imaging. Furthermore, an OR-AND-gated nanocircuit of higher complexity was designed to illustrate the versatility of our approach. The present work illustrates the potential of the use of upconversion nanotechnology as a regulatory tool for spatial and temporal control of DNA computation in cells and animals.