Pre-clinical MRI-guided intravesical instillation theranosis of bladder cancer by tumor-selective oxygen nanogenerator

Abstract

Bladder tumor intravesical instillation is usually compromised by hypoxia and low target efficiency. Herein, a nanoscale oxygen generator ([email protected]) encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) and organoselenium (SeD) with PLZ4 peptide as the BCa-targeting moiety was constructed for intravesical instillation to overcome the resistance caused by hypoxia and achieve the real-time MR imaging-guided theranosis of patient-derived bladder tumors. The real-time monitoring of intact bladders excised from 3 BCa patients showed that [email protected] could not only precisely target the tumor region inside the bladder but also specifically enhance MRI contrast efficacy. As expected, [email protected] could efficiently accumulate in BCa cells and could “infect” different batches of cells, thus enhancing its tumor permeability. Moreover, [email protected] consumed excess H2O2 inside the tumor through the Fenton reaction, which relieved hypoxia resistance and effectively inhibited the proliferation of BCa cells. Taken together, these results suggest that the nanoscale oxygen generator [email protected] hold potential for application in MRI-guided preclinical BCa theranosis by ameliorating hypoxic conditions and elevating chemotherapeutic efficacy.