A multifunctional M1-like cell vehicle to intravesically deliver ICG for photodynamic therapy of bladder cancer

  • J Control Release. 2026 Jan 10:389:114428. doi: 10.1016/j.jconrel.2025.114428.
Li Sun  1 ,  Xiaowen Qin  2 ,  Dingyi Liu  3 ,  Wenyan Zuo  3 ,  Heng Wang  3 ,  Wentao Xu  4 ,  Bin Zheng  3 ,  Qi Zhang  3 ,  Wenbin Xue  3 ,  Yang Liu  4 ,  Zhenghong Liu  3 ,  Yixuan Mou  3 ,  Yiyang Chen  3 ,  Chenkai Wang  3 ,  Xuanyi Zhou  3 ,  Dahong Zhang  5 ,  Pu Zhang  6
Affiliations
  • 1. Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310000, Zhejiang, China; Xingtai Medical Colleage, Xingtai 054000, Hebei, China.
  • 2. Department of Nutrition and Food Hygiene, The National Key Discipline, School of Public Health, Harbin Medical University, Harbin 15008, China.
  • 3. Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310000, Zhejiang, China.
  • 4. Cancer Center, Department of Interventional Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310000, Zhejiang, China.
  • 5. Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310000, Zhejiang, China. Electronic address: [email protected].
  • 6. Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310000, Zhejiang, China. Electronic address: [email protected].
PMID: 41265643 DOI: 10.1016/j.jconrel.2025.114428
Abstract

Intravesical drug delivery systems often fail to satisfy the requirement of multifunctionality in one entity, including mucoadhesion, tumor-selective binding and deep tumor-penetration. In this work, we engineered the surface of M1-like macrophages with both tumor-targeted and mucoadhesive ligands (R11) to develop a multifunctional cell vehicle (M1R11) for intravesical delivery of ICG. Remarkably, M1R11 corrected the lysosomal trafficking of ICG, directed it to enter the transcellular pathway and thereby enhance its intra-tumoral penetration. When intravesically applied, the M1R11-delivered ICG displayed much improved photodynamic efficacy, ultimately eradicating orthotopic bladder tumors in most cases and achieving complete pathological response.

Keywords
Bladder Cancer; Direct transfer; Intravesical therapy; Photodynamic therapy; Transcytosis.
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