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

• Published in: Nano today Vol. 38; p. 101124
• Main Authors: Lin, Weiqiang, Liu, Hongxing, Chen, Lingwu, Chen, Junxing, Zhang, Dong, Cheng, Qingqing, Yang, Fang, Zeng, Qinsong, Chen, Tianfeng
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.06.2021
• Subjects: Bladder cancer; Hypoxia; Magnetic resonance imaging; Patient-derived bladder; Selenium heterocycles; Hypoxia; Magnetic resonance imaging; Bladder cancer; Patient-derived bladder; Selenium heterocycles
• ISSN: 1748-0132; 1878-044X
• DOI: 10.1016/j.nantod.2021.101124

Bladder tumor intravesical instillation is usually compromised by hypoxia and low target efficiency. Herein, a nanoscale oxygen generator (PLZ4@SeD) 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 PLZ4@SeD could not only precisely target the tumor region inside the bladder but also specifically enhance MRI contrast efficacy. As expected, PLZ4@SeD could efficiently accumulate in BCa cells and could “infect” different batches of cells, thus enhancing its tumor permeability. Moreover, PLZ4@SeD 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 PLZ4@SeD hold potential for application in MRI-guided preclinical BCa theranosis by ameliorating hypoxic conditions and elevating chemotherapeutic efficacy. Constructing a nanoscale oxygen generator PLZ4@SeD to achieve real-time MR imaging-guided intravesical instillation theranosis of patient-derived bladder cancer. The nanogenerator could target bladder tumors and induce apoptosis by relieving hypoxia through consuming excess endogenous H2O2. [Display omitted] •The intact bladders excised from 3 BCa patients have been utilized to verify the MRI enhancement of PLZ4@SeD to tumor.•PLZ4@SeD enhances its anti-cancer effect through overcoming hypoxia-induced resistance by ameliorating hypoxic condition.•PLZ4@SeD selectively recognizes BCa cells and accumulates in them.