Imaging and Downstaging Bladder Cancer with the ¹⁷⁷Lu-Labeled Bioorthogonal Nanoprobe

Efforts on bladder cancer treatment have been shifting from extensive surgery to organ preservation in the past decade. To this end, we herein develop a multifunctional nanoagent for bladder cancer downstaging and bladder-preserving therapy by integrating mucosa penetration, reduced off-target effects, and internal irradiation therapy into a nanodrug. Specifically, an iron oxide nanoparticle was used as a carrier that was coated with hyaluronic acid (HA) for facilitating mucosa penetration. Dibenzocyclooctyne (DBCO) was introduced into the HA coating layer to react through bioorthogonal reaction with azide as an artificial receptor of bladder cancer cells, to improve the cellular internalization of the nanoprobe labeled with 177 Lu. Through magnetic resonance imaging, the targeted imaging of both nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) was realized after intravesical instillation of the multifunctional probe, both NMIBC and MIBC were found downstaged, and the metastasis was inhibited, which demonstrates the potential of the multifunctional nanoprobe for bladder preservation in bladder cancer treatment.