Upconversion Nanoparticle‐Covalent Organic Framework Core–shell Particles as Therapeutic Microrobots Trackable With Optoacoustic Imaging

Despite the development of various medical imaging contrast agents, integrating contrast signal generation with therapeutic and microrobotic functions remains challenging without complicated fabrication processes. In this study, upconversion nanoparticle‐covalent organic framework (UCNP‐COF) core–shell sub‐micron particles are developed that function as therapeutic microrobots trackable with multi‐spectral optoacoustic tomography (MSOT) imaging and can be loaded with desired therapeutic molecular agents in a customizable manner. The mechanism of optoacoustic signal generation in UCNP‐COF particles is attributed to the quenching of upconversion luminescence emitted by the UCNPs, which is absorbed by the encapsulating COF and subsequently converted into acoustic waves. Unlike other microparticulate agents previously imaged with MSOT, UCNP‐COF particles do not pose concerns about their stability and biocompatibility. Simultaneously, the mesoporous texture of the COF provides a large surface area, allowing for the efficient loading of various drug molecules, which can be released at target sites. Furthermore, the magnetic UCNP‐COF Janus particles can be magnetically navigated through in vivo vasculature while being visualized in real‐time with volumetric MSOT. This study proposes an approach to design photonic materials with multifunctionality, enabling high‐performance medical imaging, drug delivery, and microrobotic manipulation toward their future potential clinical use.