Intravesical delivery of mucoadhesive and tumor-selective-penetrating nanozymes for enhancing the PDT of bladder cancer

  • J Nanobiotechnology. 2025 Aug 6;23(1):554. doi: 10.1186/s12951-025-03594-6.
Yang Liu  #  1  2 ,  Wentao Xu  #  3 ,  Xiaowen Qin  #  4  5 ,  Jiajia Zheng  3  6 ,  Bin Zheng  4 ,  Li Sun  4 ,  Wenyan Zuo  4 ,  Dingyi Liu  4 ,  Zhenghong Liu  4 ,  Yixuan Mou  4 ,  Heng Wang  4 ,  Qi Zhang  4 ,  Jun Chen  7 ,  Pu Zhang  8 ,  Dahong Zhang  9  10
Affiliations
  • 1. Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China.
  • 2. Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
  • 3. Cancer Center, Department of Interventional Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
  • 4. Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
  • 5. Department of Nutrition and Food Hygiene, The National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China.
  • 6. College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
  • 7. Cancer Center, Department of Interventional Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. [email protected].
  • 8. Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. [email protected].
  • 9. Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China. [email protected].
  • 10. Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. [email protected].
  • # Contributed equally.
PMID: 40770338 DOI: 10.1186/s12951-025-03594-6
Abstract

Intravesical photodynamic therapy (PDT) emerges as a promising modality for bladder Cancer treatment, yet its efficacy is often curtailed by weak muco-adhesion, poor muco-penetration, low tumor-targeting and intra-tumoral oxygen scarcity. In this work, we introduce a drug delivery system leveraging cerium oxide (CeO2) nanozymes as the core, polyarginine peptides R11 as the tumor-targeting ligands, and indocyanine green (ICG) as the photosensitizers, with the latter two components assembled on the particle surface. Intravesical ICG@R11-CeO2 nanoparticles displayed enhanced mucoadhesive, mucus-penetrating and tumor-targeting properties, and effectively mitigated the hypoxia threat in the tumor microenvironment to improve the PDT sensitivity. Remarkably, the intravesical PDT via ICG@R11-CeO2 nanoparticles achieved complete tumor inhibition in orthotopic bladder Cancer models, offering strong evidence on its clinical translational potential.

Keywords
Bladder Cancer; Intravesical therapy; Nanozyme; Photodynamic therapy.
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