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

Weiqiang Lin,Hongxing Liu,Lingwu Chen,Junxing Chen,Dong Zhang,Qingqing Cheng,Fang Yang,Qinsong Zeng,Tianfeng Chen

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 H 2 O 2 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.