2. Academic Validation
  3. Fluorinated albumin nanocages dually target CAFs and tumor cells to potentiate bladder cancer chemoimmunotherapy

Fluorinated albumin nanocages dually target CAFs and tumor cells to potentiate bladder cancer chemoimmunotherapy

  • J Control Release. 2025 Sep 17:387:114246. doi: 10.1016/j.jconrel.2025.114246.
Zhijun Miao 1,  Anan Xu 2,  Gang Shen 1,  Siyi Tang 2,  Jie Luo 2,  Jiajian Yang 1,  Zhe Chen 3,  Jinxian Pu 4,  Tao Yang 5
Affiliations

Affiliations

  • 1 Department of Urology, The Fourth Affiliated Hospital of Soochow University, Suzhou 215000, China.
  • 2 College of Pharmaceutical Sciences, Department of Otolaryngology, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou 215006, China.
  • 3 College of Pharmaceutical Sciences, Department of Otolaryngology, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou 215006, China. Electronic address: chenzhe0322@163.com.
  • 4 Department of Urology, The Fourth Affiliated Hospital of Soochow University, Suzhou 215000, China. Electronic address: pjx62@sina.com.
  • 5 College of Pharmaceutical Sciences, Department of Otolaryngology, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou 215006, China; State Key Laboratory of Radiation Medicine and Protection, and School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China. Electronic address: tyang0920@suda.edu.cn.
PMID: 40972824 DOI: 10.1016/j.jconrel.2025.114246
Abstract

Immunogenic cell death (ICD) induced by chemotherapeutics holds promise for Cancer therapy, but limited drug penetration across the bladder mucosa and an immune-excluded tumor microenvironment (TME) have hindered success in bladder Cancer. Here, we develop fluorinated albumin nanocages as transmucosal delivery vesicles that concurrently target cancer-associated fibroblasts (CAFs) and tumor cells to potentiate chemoimmunotherapy. Surface fluorination enables mucosal penetration, while recognition of secreted protein acidic and cysteine-rich (SPARC) protein ensures selective uptake by CAFs and tumor cells. Encapsulated chemotherapeutics enhance ICD through inhibition of the Bcl-2 pathway, promoting tumor cell death. Simultaneous CAF disruption reduces stromal fibrosis, facilitating anti-PD-L1 antibody delivery and T-cell infiltration. This dual-targeting strategy synergizes ICD with immune checkpoint blockade to eradicate bladder tumors by recruiting cytotoxic T cells and suppressing immunosuppressive phenotypes. Ex vivo studies in freshly resected human bladder tumors further validated the translational potential. Our findings highlight the fluorinated albumin nanocages as a versatile transmucosal platform to remodel the tumor-stroma axis and amplify chemoimmunotherapy in bladder Cancer.

Keywords

Bladder cancer; Cancer-associated fibroblasts; Chemo-immunotherapy; Fluorinated albumin nanocages; Transmucosal delivery.

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